Biofelsefe — DNA
NFA 2020 / Aziz Yardımlı

 

Biofelsefe — DNA


DİZİN

DNA (B)
DNA (W)
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SİTE İÇİ ARAMA       
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📌 DNA Timeline



DNA yapısının incelemesi 100 yıldan daha uzun bir süre geriye gider.

 



📥 DNA molecule 3D Model

 




🛑 DNA

 
 

🛑 GENEL BAKIŞ

GENEL BAKIŞ

 

1953’te James Watson ve Francis Crick DNAnın yapısını saptadılar.

Watson ve Crick bu sonuca daha önceki çalışmalar yoluyla ulaştılar: 1928'de Frederick Griffith DNAnın genetik gereç olduğunu tanıtladı; Chargaff A-T ve G-C kurallarını buldu; Rosalind Franklin ve Maurice Wilkins DNA üzerine X-ışını kristalografisi incelemeleri yaptı ve Franklin’in X-ray imgeleri bir sarmal yapısını düşündürdü.

1869'da, Friedrich Miescher hücrelerin çekirdeğinden nuklein dediği bir tözü yalıttı. Daha sonra ögrencisi Richard Altmann aynı tözü nükleik asit olarak adlandırdı.

1929'da, Phoebus Levine DNA'nın ilk dört bazı keşfetti.



Dr. Francis Crick ve Dr. James Watson
bir Moleküler Bioloji Simpozyumunda.

“Watson was not entirely convinced of the helical structure that Franklin had suggested, and his critique of her work led her to doubt herself. Wilkins consulted with Watson and Crick. Without Franklin’s knowledge, he handed them the data that he and Franklin had worked on. Watson immediately recognized the significance. He and Crick went to work on a model of DNA.” (L — “Applications of Genetics,” by James F Frayne.)

 

📹 Watch Now — What Is DNA? / Thought.co (VİDEO)

📹 Watch Now — What Is DNA? / Thought.co (LINK)

 





Sitozinin moleküler modeli. Azotlu bazlar DNA ve RNAda bulunur.



  • DNA insanda ve başka birçok canlıda kalıtımsal bilgiyi taşıyan biolojik bir makromoleküldür.
  • DNA protein bireşimi için, hücre düzeni, metabolizması ve bölünmesi için gereklidir.
  • DNA kromatin denilen proteinler ile birlik içinde çoğunlukla hücre çekirdeğinde bulunur (mitokondri de DNA molekülleri kapsar).

 



Tümleyici baz eşleşmesi.

 

  • DNA genellikle nükleotidlerin çift-telli bir polmeridir (tek-telli DNA da vardır).
  • DNAdaki nükleotidler deoksiroz şeker, bir fosfat ve bir azotlu bazdan yapılı moleküllerdir.
  • DNAdaki azotlu bazlar dört tiptir: Adenin, Guanin, Thimin, ve Sitozin.
  • Fosfat ve deoksiriboz şeker uzun DNA molekülünün omurgasını oluşturur (bazlar bir merdivenin basamakları gibi uzanır).
  • Her bir şeker molekülün üçüncü ve beşinci karbon atomları ile bir fosfat molekülüne bağlıdır.
DNA İşlevleri


  • DNA işlevleri anlaşılmadan çok daha önce 19’uncu yüzyıl gibi erken bir tarihte keşfedildi.
  • DNA ve onunla ilişkili bir molekül olan ribonükleik asit (RNA) başlangıçta yalnızca çekirdekte bulunan asidik moleküller olarak görüldüler.
  • Mendel’in genetik üzerine deneylerinin ışığında, kalıtımın özel parçacıklar tarafından iletildiğini ve kalıtım için biokimyasal bir temelin olduğunu açığa çıktı.
  • Bir dizi deney sonucunda, hücre içindeki dört makromolekül tipi (karbohidratlar, lipidler, proteinler ve çekirdek asitleri) arasında bir kuşaktan bir sonrakine tutarlı olarak iletilen kimyasalların yalnızca çekirdek asitleri olduğu anlaşıldı.
  • DNAnın kuşaktan kuşağa aktarılan gereç olduğu anlaşıldıktan sonra işlevleri araştırılmaya başladı.

 

Hücrenin tüm etkinliklerini programlayan bilgiler DNA yapısında kodlanmış olarak bulunur.




İnsan kromozomlarının şeritli kalıpları.
Kromozomlar 1-22 yaklaşık büyüklük sırasına göre numaralıdır. Tipik bir insan hücresi bu kromozomların her birinden iki adet artı iki eşey kromozomunu kapsar—dişide iki X kromozomu ve erkekte bir X ve bir Y kromozomu. Bu haritaları yapmak üzere kullanılan kromozomlar mitozun erken bir evresinde, kromozomlar tam olarak sıkışmış değilken kullanılmıştır. Yatay kırmızı çizgi sentromerin konumunu temsil eder. Kromozomlar 13, 14, 15, 21 ve 22 üzerindeki kırmızı düğmeler büyük ribozomal RNAlar için kodlama yapan genlerin konumunu belirtir. Bu şeritli kalıplar kromozomların giemsa boyası ile boyanması yoluyla elde edilir ve ışık mikroskobu altında gözlenebilir.
(Adapted from U. Francke, Cytogenet. Cell Genet. 31:24– 32, 1981.) .

 

1) Eşlenim ve Kalıtım


 

  • Her DNA molekülü nükleotidlerinin dizisi ile ayırdedilir.
  • İnsan genomunun nükleotid dizisi saptandığı zaman, 23 çift kromozomun her birini oluşturan nükleotidlerin bir sayfa üzerindeki sözcük dizileri gibi yerleştiği görüldü.
  • Buna karşı, şeker-fosfat omurga yapısı tüm türlerin tüm DNA moleküllerine ortaktır.

 

  • Çift telli DNA molekülü eşlemleneceği zaman, ilkin çifte sarmalın iki teli kısa bir kesim boyunca ayrılır ve kabarcık gibi bir yapı oluşur.


DNA eşlenimindeki adımlara genel bir bakış.

DNA
eşlenimi kökenin çözülmesi ile başlar ve her iki DNA teli üzerinde RNA primerin (çentikli çizgiler) bireşimi tarafındna izlenir. DNA polimeraz delta ya da epsilon bu primerleri yeni DNA (yeşil çizgiler) ekleyerek yalnızca 5'—3' yönünde uzatır. Öncü teller üzerinde, bu uzun DNA moleküllerinin sürekli bireşiminde sonuçlanır. Geciken teller ise, tersine, süreksiz olarak bireştirilir; primerler her ~200 nükleotid boyunca kalıp üzerine yerleştirilir ve kısa Okozaki fragmanlarını oluşturmak üzere uzatılır. Yalınlık uğruna, bu çizge primerlerin DNA ile yer değiştirmesini ya da kromozom uçlarında telomerlerin bireşimini göstermez. (W)

 

  • Bu tek-telli geçici bölgede bir dizi enzim ve protein tümleyici teli yaratmak için çalışır.
  • Aralarında DNA polimeraz da olmak üzere, bu enzimler bütün bir DNA eşleninceye dek her bir tel boyunca çalışarak yeni bir polinükleotid molekül yaratır.

 

  • Örgenlikteki her hücre bölünmesinde çekirdekteki genetik gereç eşlemlenir.
  • Yaklaşık 3 milyar kadar nükleotid doğru olarak okunur ve eşlemlenir.
  • DNA polimerazın ve bir dizi hata onarım düzeneğinin sağınlığı her 10 milyar baz çifti için yalnızca bir nükleotidin yanlış yerleştirilmesine izin verecek denli yüksektir.
 
2) Eşyazım

 

  • Genetik gereç ikinci olarak hücrenin fizyolojik etkinliğini denetler.
  • Bedendeki katalitik ve işlevsel rollerin çoğu peptidler, proteinler ve RNA tarafından yerine getirilir.
  • Bu moleküllerin yapı ve işlevleri DNAdaki nükleotid dizileri tarafından belirlenir.



Gen anlatımı: DNA → RNA → protein.
Ökaryotik bir hücrede çekirdekte bulunan DNA sitoplazmada yer alacak olan protein üretimini programlar. Bunu ilkin iletmen RNAnın (mRNA) bireşimini belirleyerek yapar.

 

  • Bir RNA molekülünün üretilmesi gerektiğinde, ilk adım eşyazımdır.
  • DNA eşleniminde olduğu gibi, bu adım tek-telli bir bölgenin geçici oluşumu ile başlar.
  • Sonra tek-telli bölge tümleyici bir polinükleotid RNA molekülünün polimerizasyonu için kalıp olarak iş görür.
  • DNAnın iki telinden yalnızca biri eşyazıma girer (buna kalıp teli ve ötekine kodlama teli denir).
  • Eşyazım tümleyici baz eşleşmesi üzerine dayandığı için, RNA dizisi aşağı yukarı kodlayıcı tel ile aynıdır.

 

  • DNAnın büyük bölümü (insanda %98) kod barındırmaz (protein sentezi için kalıp sağlamaz).
  • Çifte zincirden her biri ötekine anti-paralel uzanır.
  • Her bir şekere dört nükleobaz tipinden biri bağlanır.
  • Bu nükleobazlar dizisi genetik bilgiyi kodlayan yapıdır.
  • Ökaryotik hücrelerde DNA kromozomlar denilen uzun yapılara örgütlenir.
  • Tipik hücre bölünmesinden önce, DNA eşlemleme sürecinde kromozomlar çiftlenir.
  • Kromozom I 220 milyon baz çifti (85 mm) ile en uzun insan kromozomudur.
  • DNAnın her iki zincirinde de nükleotid dizileri biçiminde biolojik program (genetik bilgi) depolanır.
  • İki zincir ayrılırken bilgiler eşlemlenir.

 

 

 



🛑 YAPI

YAPI

 

  • DNA birbiri çevresinde sarmal oluşturan iki polinükleotid zincirinden yapılıdır.
  • Polisakkarid, protein ve lipidlerin yanısıra, polinükleotidler dört büyük makromolekül tipinden biridir.


DNAnın yapısı: Çifte sarmal ve her bir teli oluşturan kimyasal bileşenler. DNAnın iki sarmalı zayıf hidrojen bağları ile birarada tutulur.

 

 

  • Her DNA nükleotidi bir baz (Sitozin (C), Guanin (G), Adenin (A) ya da Thimin (T)), bir şeker (deoxyriboz) ve bir fosfat grubu olmak üzere üç bileşenden oluşur.
  • Baz eşlenmesi DNA eşleminin ve DNA onarımının temelinde yatar.
  • Nükleotidler birbirine kovalent bağlar ile bağlıdır (fosfodiester bağ).
  • Bağ bir nükleotidin şekeri ve ötekinin fosfatı arasındadır.
  • Bağ DNA için değişimli fosfat—şeker—fosfat—şeker— … yapısından oluşan bir omurga sağlar.
  • İki ayrı polinükleotid zincirin azot bazları A T ile ve C G ile olmak üzere hidrojen bağları ile bağlanarak çift zincirli DNAyı oluşturur.
  • DNAnın iki zinciri birbirinin tam tümleyicisidir ve çifte sarmal merdivenin basamakları her zaman A—T ve C—G baz çiftlerinden oluşur.



Polinükleotid zincirinden parça.
Güçlü riboz-fosfat bağları insanda yaklaşık 180 cm boyunda olan molekülün uzun yapısı için sağlam bir omurga sağlarken, nükleotidler arasındaki zayıf hidrojen bağları sarmalın tellerinin kolayca ayrılmasına izin verir.

 



🛑 DNA YAPISI/DNA STRUCTURE

DNA Structure
Lippincott’s Illustrated Reviews: Biochemistry, Fifth Edition
 
 
 
Figür 29.1
Moleküler biolojinin “özeksel dogması.”
Figure 29.1
The “central dogma” of molecular biology.
 
 
Bilginin DNAdan RNAya ve ondan proteine akışına moleküler biolojinin ‘özeksel dogması” denir (Figür 29.1), ve tüm örgenlikler için betimleyicidir (genetik bilgileri için depo olarak RNA taşıyan kimi virüslerin dışlanması ile).

The flow of information from DNA to RNA to protein is termed the “central dogma” of molecular biology (Figure 29.1), and is descriptive of all organisms, with the exception of some viruses that have RNA as the repository of their genetic information.


I. GENEL BAKIŞ
Nükleik asitler genetik bilginin depolanması ve anlatımı için gereklidir. Kimyasal olarak ayrı iki nükleik asit tipi vardır: Deoksiribonükleik asit (DNA) ve ribonükleik asit (RNA). DNA genetik bilginin deposudur ve yalnızca ökaryotik örgenliklerin çekirdeklerindeki kromozomlarda değil, ama bitkilerin mitokondri ve kloroplastlarında da bulunur. Çekirdekten yoksun prokaryotik hücrelerin tek bir kromozomları vardır, ama plasmidler biçiminde kromozomal-olmayan DNA da kapsayabilirler. DNAda bulunan genetik bilgi DNA eşlemesi yoluyla eşlemlenerek yeni hücrelere iletilir. Döllenmiş bir yumurtada kapsanan DNA bir örgenliğin gelişimini yöneten bilgiyi kodlandırır. Bu gelişme milyarlarca hücrenin üretimine götürebilir. Her bir hücre özelleşmiştir ve yalnızca örgenliği sürdürmede rolünü yerine getirmesi için gerekli olan işlevleri anlatabilir. Buna göre, DNA bir hücrenin bölündüğü her keresinde tam eşleme yapabilmekle kalmamalı, ama kapsadığı bilginin seçici olarak anlatılmasını da sağlamalıdır. RNA eşlemlemesi (transcription) genetik bilginin anlatımında ilk evredir. Sonra, iletmen RNAnın nükleotid dizisinde kapsanan kod çevrilir (protein bireşimi), böylece genetik anlatımı tamamlanır.

 

I. OVERVIEW
Nucleic acids are required for the storage and expression of genetic information. There are two chemically distinct types of nucleic acids: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA, the repository of genetic information, is present not only in chromosomes in the nucleus of eukaryotic organisms, but also in mitochondria and the chloroplasts of plants. Prokaryotic cells, which lack nuclei, have a single chromosome, but may also contain nonchromosomal DNA in the form of plasmids. The genetic information found in DNA is copied and transmitted to daughter cells through DNA replication. The DNA contained in a fertilized egg encodes the information that directs the development of an organism. This development may involve the production of billions of cells. Each cell is specialized, expressing only those functions that are required for it to perform its role in maintaining the organism. Therefore, DNA must be able to not only replicate precisely each time a cell divides, but also to have the information that it contains be selectively expressed. Transcription (RNA synthesis) is the first stage in the expression of genetic information (see Chapter 30). Next, the code contained in the nucleotide sequence of messenger RNA molecules is translated (protein synthesis), thus completing gene expression.

 


Figür 29.2
A. 5'→ 3' yönünde yazılı olarak gösterilen nükleotid dizisi ile DNA zinciri. Bir 3' →5'-fosfodiester bağı mavi kutuda gösterilmiş, ve deoksiriboz-fosfat omurgası sarı renkli alandadır.
B. Daha stilize biçimde yazılı DNA zinciri riboz-fosfat omurgayı öne çıkarmaktadır.
C. Nükleotid dizisinin daha yalın bir temsili.
D. En yalın (ve en yaygın) temsilde bazlar için kısaltmalar uylaşımsal 5'→3' yönünde yazılmıştır.

 
Figure 29.2
A. DNA chain with the nucleotide sequence shown written in the 5'→ 3' direction. A 3' →5'-phosphodiester bond is shown highlighted in the blue box, and the deoxyribose-phosphate backbone is shaded in yellow.
B. The DNA chain written in a more stylized form, emphasizing the ribose–phosphate backbone.
C. A simpler representation of the nucleotide sequence.
D. The simplest (and most common) representation, with the abbreviations for the bases written in the conventional 5'→3' direction.


 

II. DNA YAPISI
DNA 3'→5'–fosfodiester bağları ile kovalent tarzında bağlanmış bir deoksiribonükleosid monofosfat polimeridir. Tekil-telli (ss: single-stranded) DN kapsayan birkaç virüs dışında, DNA çift-telli (ds: double-stranded) molekül olarak bulunur ve yapısındaki iki tel birbiri çevresine dolanarak bir çifte sarmal oluşturur. Ökaryotik hücrelerde, DNA nükleusta bulunan çeşitli protein tipleri (ortak bir adlandırma ile nükleoprotein olarak bilinirler) ile bağlantı içinde bulunur. Prokaryotlarda ise protein-DNA karmaşası nükleoid olarak bilinen bir membran-bağlantısız bir bölgede bulunur.

 

II. STRUCTURE OF DNA
DNA is a polymer of deoxyribonucleoside monophosphates covalently linked by 3'→5'–phosphodiester bonds. With the exception of a few viruses that contain single-stranded (ss) DNA, DNA exists as a doublestranded (ds) molecule, in which the two strands wind around each other, forming a double helix. In eukaryotic cells, DNA is found associated with various types of proteins (known collectively as nucleoprotein) present in the nucleus, whereas in prokaryotes, the protein–DNA complex is present in a nonmembrane-bound region known as the nucleoid.


A. 3'→5'-Fosfodiester bağları
Fosfodiester bağları bir nükleotidin deoksipentozunun 3'-hidroksil grubunu bir fosfat grubu yoluyla bitişik nükleotidin deoksipentozunun 5'-hidroksil grubu ile birleştirir (Figür 29.2). Sonuçta ortaya çıkan uzun, dalsız zincir kutupsallık gösterir ve başka nükleotidlere bağlanmış olmayan bir 5'-uç (serbest fosfatlı) ve bir de 3'-uç (serbest hidroksilli) taşır. Ortaya çıkan deoksiriboz-fosfat omurgası boyunca yerleşen bazlar uylaşımsal olarak her zaman zincirin 5'-ucundan 3'-ucuna doğru dizili olarak yazılır. Örneğin Figür 29.2'de gösterilen DNAdaki bazlar dizisi "thimin, adenin, sitozin, guanin" olarak okunur (5'-TACG-3'). Nükleotidler (DNA ya da RNAdaki) arasındaki fosfodiester bağlantılar kimyasallar tarafından hidrolitik olarak yarılabilir, ya da bir nükeazlar ailesi tarafından enzimatik olarak hidrolize edilebilir: DNA için deoksiribonükleazlar ve RNA için ribonükleazlar. [Not: Yalnızca RNA alkali tarafından yarılır.]

 

A. 3'→5'-Phosphodiester bonds
Phosphodiester bonds join the 3'-hydroxyl group of the deoxypentose of one nucleotide to the 5'-hydroxyl group of the deoxypentose of an adjacent nucleotide through a phosphate group (Figure 29.2). The resulting long, unbranched chain has polarity, with both a 5'-end (the end with the free phosphate) and a 3'-end (the end with the free hydroxyl) that are not attached to other nucleotides. The bases located along the resulting deoxyribose–phosphate backbone are, by convention, always written in sequence from the 5'-end of the chain to the 3'-end. For example, the sequence of bases in the DNA shown in Figure 29.2 is read “thymine, adenine, cytosine, guanine” (5'-TACG-3'). Phosphodiester linkages between nucleotides (in DNA or RNA) can be cleaved hydrolytically by chemicals, or hydrolyzed enzymatically by a family of nucleases: deoxyribonucleases for DNA and ribonucleases for RNA. [Note: Only RNA is cleaved by alkali.]

 
 
Figür 29.3
DNA çifte sarmalı ve kimi önemli yapısal özellikleri.
Figure 29.3
DNA double helix, illustrating some
of its major structural features.
 
   

B. Çifte sarmal
Çifte sarmalda iki zincir simetri ekseni denilen ortak bir eksen çevresinde sarımlanır. Zincirler antiparalel bir tarzda çiftlenir ve buna göre bir telin 5'-ucu ötekin telin 3'-teli ile çiftlenir (Figür 29.3). DNA sarmalında her bir zincirin hidrofilik deoksiriboz-fosfat omurgası molekülün dışında iken, hidrofobik bazlar içeride yığılmışır. Bütününde yapı bükülmüş bir merdiveni andırır. Sarmaldaki iki tel arasındai uzaysal ilişki bir büyük (geniş) ve bir de küçük (dar) oluk yaratır. Bu oluklar düzenleyici proteinlerin DNZ zinciri boyunca özgül tanıma dizilerine bağlanması için giriş sağlar. Belli anti-kanser ilaçları, örneğin daktinomisin (aktinomisin D), sitotoksik etkilerini DNA çifte sarmalarının dar oluğuna girerek ve böylece DNA ve RNA bireşimine engel olarak uygular.

 

B. Double helix
In the double helix, the two chains are coiled around a common axis called the axis of symmetry. The chains are paired in an antiparallel manner, that is, the 5'-end of one strand is paired with the 3'-end of the other strand (Figure 29.3). In the DNA helix, the hydrophilic deoxyribose–phosphate backbone of each chain is on the outside of the molecule, whereas the hydrophobic bases are stacked inside. The overall structure resembles a twisted ladder. The spatial relationship between the two strands in the helix creates a major (wide) groove and a minor (narrow) groove. These grooves provide access for the binding of regulatory proteins to their specific recognition sequences along the DNA chain. Certain anticancer drugs, such as dactinomycin (actinomycin D), exert their cytotoxic effect by intercalating into the narrow groove of the DNA double helix, thus interfering with DNA and RNA synthesis.

 
 
Figür 29.4
İki tümleyici DNA dizisi.
Figure 29.4
Two complementary DNA
sequences.
 
   
     

1. Baz çiftlenmesi: Bir DNA telinin bazları ikinci telin bazları ile çiftlenir, öyle bir yolda ki bir adenin her zaman bir thimin ve bir sitozin her zaman bir guanin ile çiftlenir. [Not: Baz çiftleri sarmalın eksenine diktir (bkz. Figür 29.3).] Buna göre, DNA çifte sarmalının bir polinükleotid zinciri her zaman ötekinin bileşenidir. Bir zincirdeki bazlar dizisi verildiğinde, tümleyici zincirdeki bazlar dizisi belirlenebilir (Figür 29.4). [Not: DNAdaki özgül baz çiftlenmesi Chargaff Kuralına götürür: Herhangi bir dsDNA örneğinde, adenin miktarı thimin miktarına, guanin miktarı sitozin miktarına eşittir, ve total pürin miktarı total pyrimidin miktarına eşittir.] Baz çiftleri hidrojen bağları ile birarada tutulur: A ve T arasında iki ve G ve C arasında üç (Figür 29.5). Bu hidrojen bağları, artı yığılı bazlar arasındaki hidrofobik etkileşimler, çifte sarmalın yapısını kararlı kılar.

 

1. Base pairing: The bases of one strand of DNA are paired with the bases of the second strand, so that an adenine is always paired with a thymine and a cytosine is always paired with a guanine. [Note: The base pairs are perpendicular to the axis of the helix (see Figure 29.3).] Therefore, one polynucleotide chain of the DNA double helix is always the complement of the other. Given the sequence of bases on one chain, the sequence of bases on the complementary chain can be determined (Figure 29.4). [Note: The specific base pairing in DNA leads to the Chargaff Rule: In any sample of dsDNA, the amount of adenine equals the amount of thymine, the amount of guanine equals the amount of cytosine, and the total amount of purines equals the total amount of pyrimidines.] The base pairs are held together by hydrogen bonds: two between A and T and three between G and C (Figure 29.5). These hydrogen bonds, plus the hydrophobic interactions between the stacked bases, stabilize the structure of the double helix.

 
 
Figür 29.5
Tümleyici bazlar arasındaki hidrojen bağları
Figure 29.5
Hydrogen bonds between
complementary bases.
 
 
 
Figür 29.6
Değişik nükleotid bileşimleri olan DNA moleküllerinin erime sıcaklıkları. (260 nm dalgaboyu ile, tekil-telli DNAnın göreli olarak çift-telli DNAdan daha yüksek bir soğrulma oranı vardır.)
Figure 29.6
Melting temperatures (Tm) of DNA
molecules with different nucleotide
compositions. (At a wavelength of
260 nm, single-stranded DNA has
a higher relative absorbance than
does double-stranded DNA.)
 
     
 
2. Çifte sarmaldaki iki DNA telinin ayrılması: Çifte sarmalın iki teli çiftlenmiş bazlar arasındaki hidrojen bağları bozulunca ayrılır. Bozulma eğer DNA çözeltisinin pHsı değiştirilir ve bu nedenle nükleotid bazlar ionlaşırsa, ya da eğer çözelti ısıtılırsa olabilir. [Not: Fosfodiester bağları bu işlem nedeniyle kopmaz.] DNA ısıtıldığı zaman, sarmal yapının yarısının yitirildiği sıcaklık derecesi ergime sıcaklığı (Tm: melting temperature) olarak tanımlanır. DNAdaki sarmal yapının yitişi (ki buna denaturasion denir) 260 nmde soğrulması ölçülerek gözlenebilir. [Not: ssDNAnın bu dalgaboyunda göreli olarak dsDNAdan daha yüksek bir soğrulma oranı vardır.] G ve C arasında üç ama A ve T arasında yalnızca iki hidrojen bağı olduğu için, daha yüksek A ve T yoğunlukları kapsayan DNA G- ve C-varsıl DNAdan daha düşük bir derecede denaturalize olur (Figür 29.6). Uygun koşullar altında, tümleyici DNA telleri renaturasion (ya da reannealing) denilen süreç yoluyla çifte sarmalı yeniden oluşturabilir.
 
2. Separation of the two DNA strands in the double helix: The two strands of the double helix separate when hydrogen bonds between the paired bases are disrupted. Disruption can occur in the laboratory if the pH of the DNA solution is altered so that the nucleotide bases ionize, or if the solution is heated. [Note: Phosphodiester bonds are not broken by such treatment.] When DNA is heated, the temperature at which one half of the helical structure is lost is defined as the melting temperature (Tm). The loss of helical structure in DNA, called denaturation, can be monitored by measuring its absorbance at 260 nm. [Note: ssDNA has a higher relative absorbance at this wavelength than does dsDNA.] Because there are three hydrogen bonds between G and C but only two between A and T, DNA that contains high concentrations of A and T denatures at a lower temperature than G- and C-rich DNA (Figure 29.6). Under appropriate conditions, complementary DNA strands can reform the double helix by the process called renaturation (or reannealing).
 
 
Figür 29.7
B-DNA ve Z-DNA yapıları.
Figure 29.7
Structures of B-DNA and Z-DNA.
 
   
 

3. Çifte sarmalın yapısal biçimleri: DNAnın üç yapısal biçimi vardır: Watson ve Crick tarafından 1953'te betimlenen B biçimi, A biçimi, ve Z biçimi. B biçimi sarmalın her 360° dönüşü için on artık ile, ve baz düzlemlerinin sarmal eksenine dikey olması ile, sağa-dönen sarmaldır. Kromozomal DNAnın birincil olarak B-DNAdan oluştuğu düşünülür (Figür 29.7 B-DNAnın uzay-dolduran bir modelini örneklendirir). A biçimi B biçiminin ılımlı olarak dehidrate edilmesi ile üretilir. O da sağa-dönen sarmaldır, ama her dönüş için 11 baz çifti vardır, ve baz çiftlerinin düzlemleri sarmal eksenine dikeyden 20° uzağa eğiktir. DNA—RNA hibridlerde ya da RNA—RNA çift-telli bölgelerde bulunan uygunluk büyük olasılıkla A biçimine çok yakındır. Z-DNA sola-dönen sarmaldır ve her dönüşte 12 kadar baz çifti kapsar (bkz. Figür 29.7). [Not: Deoksiriboz “zigzag yapar“ ve “Z”-DNA adı buradan gelir.] Z-DNA kesimler DNAnın değişimli pürin ve pyrimidin dizilerinin olduğu bölgelerinde doğallıkla ortaya çıkar, örneğin poli GC. DNAnın B ve Z sarmal biçimleri arasında geçişler gen anlatımının düzenlemesinde rol oynuyor olabilir.

 
3. Structural forms of the double helix: There are three major structural forms of DNA: the B form, described by Watson and Crick in 1953, the A form, and the Z form. The B form is a right-handed helix with ten residues per 360° turn of the helix, and with the planes of the bases perpendicular to the helical axis. Chromosomal DNA is thought to consist primarily of B-DNA (Figure 29.7 illustrates a space-filling model of B-DNA). The A form is produced by moderately dehydrating the B form. It is also a right-handed helix, but there are 11 base pairs per turn, and the planes of the base pairs are tilted 20° away from the perpendicular to the helical axis. The conformation found in DNA–RNA hybrids or RNA–RNA double-stranded regions is probably very close to the A form. Z-DNA is a left-handed helix that contains about 12 base pairs per turn (see Figure 29.7). [Note: The deoxyribose–phosphate backbone “zigzags,” hence, the name “Z”-DNA.] Stretches of Z-DNA can occur naturally in regions of DNA that have a sequence of alternating purines and pyrimidines, for example, poly GC. Transitions between the B and Z helical forms of DNA may play a role in regulating gene expression.
 

C. Doğrusal ve dairesel DNA molekülleri
Bir ökaryotun çekirdeğindeki her bir kromozom tek bir uzun, doğrusal dsDNA molekülü kapsar ve bu kromatin oluşturmak üzere proteinler karışımından (histon ve histon-olmayan) oluşan bir karmaşaya bağlıdır. Ökaryotlar, bitki kloroplastları gibi, mitokondrilerinde kapalı, dairesel DNA molekülleri kapsar. Prokaryotik bir örgenlik tipik olarak tekil, çift-telli, süper-büklümlü, dairesel bir kromozom kapsar. Her bir prokaryotik kromozom DNAyı bir nükleoid oluşturmak üzere yoğunlaştırabilen histon-olmayan proteinler ile birliktedir. Ek olarak, bakteri türlerinin çoğu da plasmidler denilen küçük, dairesel, ektra-kromozomal DNA molekülleri kapsar. Plasmid DNA genetik bilgi taşır, ve kromozomal bölünme ile senkronize olabilen ya da olmayabilen eşlemlemeye uğrar.

 
C. Linear and circular DNA molecules
Each chromosome in the nucleus of a eukaryote contains one long, linear molecule of dsDNA, which is bound to a complex mixture of proteins (histone and non-histone, see p. 409) to form chromatin. Eukaryotes have closed, circular DNA molecules in their mitochondria, as do plant chloroplasts. A prokaryotic organism typically contains a single, double-stranded, supercoiled, circular chromosome. Each prokaryotic chromosome is associated with non-histone proteins that can condense the DNA to form a nucleoid. In addition, most species of bacteria also contain small, circular, extrachromosomal DNA molecules called plasmids. Plasmid DNA carries genetic information, and undergoes replication that may or may not be synchronized to chromosomal division.

 



 

 



📹 DNA Replication — Leading Strand vs Lagging Strand & Okazaki Fragments / The Organic Chemistry Tutor (VİDEO)

📹 DNA Replication — Leading Strand vs Lagging Strand & Okazaki Fragments / The Organic Chemistry Tutor (LINK)

This biology video tutorial provides a basic introduction into DNA replication. It discusses the difference between the leading strand and the lagging strand as well as the presence of okazaki fragments. Here is a list of topics:
0:00
- Intro to DNA Replication
0:00
- Semiconservative Replication
0:49
- DNA strands are antiparallel
1:07
- Complementary Base Pairing In DNA
2:05
- Hydrogen Bonds Between Adenine, Thymine, Cytosine, and Guanine In DNA
2:39
- Bidirectionality of DNA and Origin of Replication
3:26
- DNA Helicase and Topoisomerase
4:30 - Single Stranded Binding (SSB) Proteins
4:53 - RNA Primers and Primase
5:27 - DNA Polymerase III
5:49
- Semidiscontinuous Nature of DNA Replication
6:40 - Leading Strand and Lagging Strand
9:00
- Okazaki Fragments
9:13 - The Function of DNA Ligase
9:30 - Exonuclease Activity of DNA Polymerase I and III - Proofreading Ability and DNA Repair

 



📹📹📹 DNA (VİDEO)

📹 The Structure of DNA (VİDEO)

📹 The Structure of DNA (LINK)

An exploration of the structure of deoxyribonucleic acid, or DNA.

 



📹 DNA Topology (VİDEO)

📹 DNA Topology (LINK)

An exploration of the complicated world of DNA topology: how DNA is described with linking number, twist, and writhe, and how topoisomerases and gyrases alter these properties.

 



📹 What is DNA Structure? (VİDEO)

📹 What is DNA Structure? (LINK)

DNA is a double-helix - it looks like a twisted ladder. Its backbone is made of sugars (deoxyribose) and phosphate groups, and the rungs of the ladder are made from 4 nitrogenous bases: Guanine, Adenine, Thymine, and Cytosine. The order of the “rungs,” or bases, is what determines what the DNA is coding for. Think of it like the order of letters in a word, and the order of words in a sentence. Except in the language of DNA, there are only 4 letters.

In this video, we discuss the structure of DNA — how big is it, how are the components attached to each other, and what is the spacing between the rungs. We’ll also learn about the major groove and minor groove, and other important details about DNA structure.

 



📹 DNA Deoxyribonucleic Acid (DNA) / Beverly (VİDEO)

📹 DNA Deoxyribonucleic Acid (DNA) / Beverly Biology (LINK)

Topics:
- Nucleotides
- Sugar
- Phosphate
- Nitrogen Base
- James Watson
- Francis Crick
- Rosalind Franklin
- Double helix
- A/T and C/G
- DNA replication
- DNA helicase
- DNA polymerase

 



 

 



  DNA (short) (B)

DNA (B)

DNA (B)

DNA (B)

DNA (B)


DNA, abbreviation of deoxyribonucleic acid, organic chemical of complex molecular structure that is found in all prokaryotic and eukaryotic cells and in many viruses. DNA codes genetic information for the transmission of inherited traits.


📹 Learn how Francis Crick and James Watson revolutionized genetics by discerning DNA's structure (VİDEO)

📹 Learn how Francis Crick and James Watson revolutionized genetics by discerning DNAs structure (LINK)

Learn how Francis Crick and James Watson revolutionized genetics by discerning DNA's structureThis video introduces the basics of DNA, the chemical that underlies life on Earth.

 





The chemical DNA was first discovered in 1869, but its role in genetic inheritance was not demonstrated until 1943. In 1953 James Watson and Francis Crick, aided by the work of biophysicists Rosalind Franklin and Maurice Wilkins, determined that the structure of DNA is a double-helix polymer, a spiral consisting of two DNA strands wound around each other. The breakthrough led to significant advances in scientists’ understanding of DNA replication and hereditary control of cellular activities.



Polynucleotide chain of deoxyribonucleic acid (DNA)
Portion of polynucleotide chain of deoxyribonucleic acid (DNA). The inset shows the corresponding pentose sugar and pyrimidine base in ribonucleic acid (RNA).



Each strand of a DNA molecule is composed of a long chain of monomer nucleotides. The nucleotides of DNA consist of a deoxyribose sugar molecule to which is attached a phosphate group and one of four nitrogenous bases: two purines ( adenine and guanine) and two pyrimidines ( cytosine and thymine). The nucleotides are joined together by covalent bonds between the phosphate of one nucleotide and the sugar of the next, forming a phosphate-sugar backbone from which the nitrogenous bases protrude. One strand is held to another by hydrogen bonds between the bases; the sequencing of this bonding is specific—i.e., adenine bonds only with thymine, and cytosine only with guanine.

📹 Explore Paul Rothemund's DNA origami and its future application in medical diagnostics, drug delivery, tissue engineering, energy, and the environment (VİDEO)

📹 Explore Paul Rothemund's DNA origami and its future application in medical diagnostics, drug delivery, tissue engineering, energy, and the environment (LINK)

Explore Paul Rothemund's DNA origami and its future application in medical diagnostics, drug delivery, tissue engineering, energy, and the environment

DNA origami, developed by American computer scientist and bioengineer Paul Rothemund, involves folding DNA to create various shapes and structures, which may be of use to scientific investigations in a wide range of fields.Science in Seconds (www.scienceinseconds.com) (A Britannica Publishing Partner)

 





The configuration of the DNA molecule is highly stable, allowing it to act as a template for the replication of new DNA molecules, as well as for the production (transcription) of the related RNA (ribonucleic acid) molecule. A segment of DNA that codes for the cell’s synthesis of a specific protein is called a gene.

DNA replicates by separating into two single strands, each of which serves as a template for a new strand. The new strands are copied by the same principle of hydrogen-bond pairing between bases that exists in the double helix. Two new double-stranded molecules of DNA are produced, each containing one of the original strands and one new strand. This “semiconservative” replication is the key to the stable inheritance of genetic traits.




The initial proposal of the structure of DNA by James Watson and Francis Crick, which was accompanied by a suggestion on the means of replication.

 

Within a cell, DNA is organized into dense protein-DNA complexes called chromosomes. In eukaryotes, the chromosomes are located in the nucleus, although DNA also is found in mitochondria and chloroplasts. In prokaryotes, which do not have a membrane-bound nucleus, the DNA is found as a single circular chromosome in the cytoplasm. Some prokaryotes, such as bacteria, and a few eukaryotes have extrachromosomal DNA known as plasmids, which are autonomous, self-replicating genetic material. Plasmids have been used extensively in recombinant DNA technology to study gene expression.


📹 t View researchers at Anthropological Institute in Göttingen studying on the world's oldest DNA family tree taken from Bronze Age found in Lichtenstein Cave, Harz mountains (VİDEO)

📹 View researchers at Anthropological Institute in Göttingen studying on the world's oldest DNA family tree taken from Bronze Age found in Lichtenstein Cave, Harz mountains (LINK)

View researchers at Anthropological Institute in Göttingen studying on the world's oldest DNA family tree taken from Bronze Age found in Lichtenstein Cave, Harz mountains

Anthropologists examine the DNA taken from Bronze Age skeletons found in Lichtenstein Cave, Harz mountains, northern Germany.Contunico © ZDF Enterprises GmbH, Mainz

 





The genetic material of viruses may be single- or double-stranded DNA or RNA. Retroviruses carry their genetic material as single-stranded RNA and produce the enzyme reverse transcriptase, which can generate DNA from the RNA strand. Four-stranded DNA complexes known as G-quadruplexes have been observed in guanine-rich areas of the human genome.

 



 







 
  DNA (W)

BAŞLIK

DNA (W)



The structure of the DNA double helix. The atoms in the structure are colour-coded by element and the detailed structures of two base pairs are shown in the bottom right.
 
 
 
Introduction

Introduction

Introduction (W)

🎨 The structure of part of a DNA double helix

 



 
   

Deoxyribonucleic acid (DNA) is a molecule composed of two polynucleotide chains that coil around each other to form a double helix carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides),nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

The two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases (cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group.The nucleotides are joined to one another in a chain by covalent bonds (known as the phospho-diester linkage) between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, pyrimidines and purines. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine.

Both strands of double-stranded DNA store the same biological information. This information is replicated as and when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences. The two strands of DNA run in opposite directions to each other and are thus antiparallel.Attached to each sugar is one of four types of nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription, where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes uracil (U). Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation.

Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms (animals, plants, fungi and protists) store most of their DNA inside the cell nucleus as nuclear DNA, and some in the mitochondria as mitochondrial DNA or in chloroplasts as chloroplast DNA. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm, in circular chromosomes. Within eukaryotic chromosomes, chromatin proteins, such as histones, compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

DNA was first isolated by Friedrich Miescher in 1869. Its molecular structure was first identified by Francis Crick and James Watson at the Cavendish Laboratory within the University of Cambridge in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, who was a post-graduate student of Rosalind Franklin at King's College London. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials.

 



 
Properties

Properties

Properties (W)

 



Chemical structure of DNA; hydrogen bonds shown as dotted lines.
 
   

DNA is a long polymer made from repeating units called nucleotides, each of which is usually symbolized by a single letter: either A, T, C, or G. The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, and have the same pitch of 34 angstroms (Å) (3.4 nanometres). The pair of chains has a radius of 10 angstroms (1.0 nanometre). According to another study, when measured in a different solution, the DNA chain measured 22 to 26 angstroms wide (2.2 to 2.6 nanometres), and one nucleotide unit measured 3.3 Å (0.33 nm) long. Although each individual nucleotide is very small, a DNA polymer can be very large and contain hundreds of millions, such as in chromosome 1. Chromosome 1 is the largest human chromosome with approximately 220 million base pairs, and would be 85 mm long if straightened.

DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together. These two long strands coil around each other, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside, and a base linked to a sugar and to one or more phosphate groups is called a nucleotide. A biopolymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.

The backbone of the DNA strand is made from alternating phosphate and sugar groups. The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These are known as the 3′-end (three prime end), and 5′-end (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers directionality (sometimes called polarity) to each DNA strand. In a nucleic acid double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA.

The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine, forming A-T and G-C base pairs.

 



Nucleobase classification

Nucleobase classification (W)

The nucleobases are classified into two types: the purines, A and G, which are fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T. A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.

 



Non-canonical bases

Non-canonical bases (W)

Modified bases occur in DNA. The first of these recognised was 5-methylcytosine, which was found in the genome of Mycobacterium tuberculosis in 1925. The reason for the presence of these noncanonical bases in bacterial viruses (bacteriophages) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses. Modifications of the bases cytosine and adenine the more common and modified DNA bases plays vital roles in the epigenetic control of gene expression in plants and animals.

 



Listing of non-canonical bases found in DNA

Listing of non-canonical bases found in DNA (W)

A number of non canonical bases are known to occur in DNA. Most of these are modifications of the canonical bases plus uracil.

  • Modified Adenosine
    • N6-carbamoyl-methyladenine
    • N6-methyadenine
  • Modified Guanine
    • 7-Deazaguanine
    • 7-Methylguanine
  • Modified Cytosine
    • N4-Methylcytosine
    • 5-Carboxylcytosine
    • 5-Formylcytosine
    • 5-Glycosylhydroxymethylcytosine
    • 5-Hydroxycytosine
    • 5-Methylcytosine
  • Modified Thymidine
    • α-Glutamythymidine
    • α-Putrescinylthymine
  • Uracil and modifications
    • Base J
    • Uracil
    • 5-Dihydroxypentauracil
    • 5-Hydroxymethyldeoxyuracil
  • Others
    • Deoxyarchaeosine
    • 2,6-Diaminopurine

 



Grooves

Grooves (W)



DNA major and minor grooves. The latter is a binding site for the Hoechst stain dye 33258.
 
   

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. One groove, the major groove, is 22 angstroms (Å) wide and the other, the minor groove, is 12 Å wide. The width of the major groove means that the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

 



Base pairing

Base pairing (W)

 
   


Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.
 
   
Further information: Base pair

In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a Watson-Crick base pair. DNA with high GC-content is more stable than DNA with low GC-content. A Hoogsteen base pair is a rare variation of base-pairing. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature. As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms.

As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart — a process known as melting — to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.

In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break half of the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.

 



Sense and antisense

Sense and antisense (W)

Further information: Sense (molecular biology)

A DNA sequence is called a “sense” sequence if it is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the “antisense” sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.

 



Supercoiling

Supercoiling (W)

Further information: DNA supercoil

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.

 



Alternative DNA structures

Alternative DNA structures (W)



From left to right, the structures of A, B and Z DNA.
 
   
Further information: Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid, Molecular models of DNA, and DNA structure

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, and the presence of polyamines in solution.

The first published reports of A-DNA X-ray diffraction patterns—and also B-DNA—used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. An alternative analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.

Although the B-DNA form is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription. A 2020 study concluded that DNA turned right-handed due to ionization by cosmic rays.

 



Alternative DNA chemistry

Alternative DNA chemistry (W)

For many years, exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1, was announced, though the research was disputed, and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.

 



Quadruplex structures

Quadruplex structures (W)



DNA quadruplex formed by telomere repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix. The green spheres in the center represent potassium ions.
 
   
Further information: G-quadruplex

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases, known as a guanine tetrad, form a flat plate. These flat four-base units then stack on top of each other to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.

 



Branched DNA

Branched DNA (W)



Branched DNA can form networks containing multiple branches.
 
   
Further information: Branched DNA and DNA nanotechnology

In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible. Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

 



Artificial bases

Artificial bases (W)

Main article: Nucleic acid analogue

Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named Hachimoji DNA. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence implies that there is nothing special about the four natural nucleobases that evolved on Earth.

 



 
Chemical modifications and altered DNA packaging

Base modifications and DNA packaging

Base modifications and DNA packaging (W)

Further information: DNA methylation and Chromatin remodeling

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.

     

cytosine

5-methylcytosine

thymine
Structure of cytosine with and without the 5-methyl group. Deamination converts 5-methylcytosine into thymine.
 

For one example, cytosine methylation produces 5-methylcytosine, which is important for X-inactivation of chromosomes. The average level of methylation varies between organisms—the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations. Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain, and the glycosylation of uracil to produce the "J-base" in kinetoplastids.

 



Damage

Damage (W)

DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. A typical human cell contains about 150,000 bases that have suffered oxidative damage. Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations. These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer. DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.



covalent adduct between a metabolically activated form of benzo[a]pyrene, the major mutagen in tobacco smoke, and DNA.
 
   

Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen. Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication. Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.

 



 
Biological functions

Biological functions

Biological functions (W)



Location of eukaryote nuclear DNA within the chromosomes.
 
   

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.

 



Genes and genomes

Genes and genomes (W)

Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which control transcription of the open reading frame.



T7 RNA polymerase
 (blue) producing an mRNA (green) from a DNA template (orange).
 
   

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences. The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species, represent a long-standing puzzle known as the "C-value enigma". However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.

Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes. An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.

 



Transcription and translation

Transcription and translation (W)

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA, and TAG codons.

 



Replication

Replication (W)

Further information: DNA replication

Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix. In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

 

DNA replication: The double helix is unwound by a helicase and topo­iso­merase. Next, one DNA polymerase produces the leading strand copy. Another DNA polymerase binds to the lagging strand. This enzyme makes discontinuous segments (called Okazaki fragments) before DNA ligase joins them together.

 



Extracellular nucleic acids

Extracellular nucleic acids (W)

Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L. Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer; it may provide nutrients; and it may act as a buffer to recruit or titrate ions or antibiotics. Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm; it may contribute to biofilm formation; and it may contribute to the biofilm's physical strength and resistance to biological stress.

Cell-free fetal DNA is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus.

Under the name of environmental DNA eDNA has seen increased use in the natural sciences as a survey tool for ecology, monitoring the movements and presence of species in water, air, or on land, and assessing an area's biodiversity.

 



 
Interactions with proteins

Interactions with proteins

Interactions with proteins (W)

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

 



DNA-binding proteins

DNA-binding proteins (W)

Further information: DNA-binding protein

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation, and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.

 

Interaction of DNA (in orange) with histones (in blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA.
 

A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.



The lambda repressor helix-turn-helix transcription factor bound to its DNA target.
 
   

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes. Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.

 



DNA-modifying enzymes

DNA-modifying enzymes (W)

No text.

 



Nucleases and ligases

Nucleases and ligases (W)



The restriction enzyme EcoRV (green) in a complex with its substrate DNA.
 
   

Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5′-GATATC-3′ and makes a cut at the horizontal line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system. In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.

Enzymes called DNA ligases can rejoin cut or broken DNA strands. Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.

 



Topoisomerases and helicases

Topoisomerases and helicases (W)

Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break. Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix. Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.

Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands. These enzymes are essential for most processes where enzymes need to access the DNA bases.

 



Polymerases

Polymerases (W)

Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products is created based on existing polynucleotide chains—which are called templates. These enzymes function by repeatedly adding a nucleotide to the 3′ hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5′ to 3′ direction. In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ exonuclease activity is activated and the incorrect base removed. In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.

RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres. For example, HIV reverse transcriptase is an enzyme for AIDS virus replication. Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. It synthesizes telomeres at the ends of chromosomes. Telomeres prevent fusion of the ends of neighboring chromosomes and protect chromosome ends from damage.

Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.

 



 
Genetic recombination

Genetic recombination

Genetic recombination (W)

A DNA helix usually does not interact with other segments of DNA, and in human cells, the different chromosomes even occupy separate areas in the nucleus called "chromosome territories". This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins. Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.

 
 
   


Structure of the Holliday junction intermediate in genetic recombination. The four separate DNA strands are coloured red, blue, green and yellow.
 
The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51. The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA. A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA. Only strands of like polarity exchange DNA during recombination. There are two types of cleavage: east-west cleavage and north–south cleavage. The north–south cleavage nicks both strands of DNA, while the east–west cleavage has one strand of DNA intact. The formation of a Holliday junction during recombination makes it possible for genetic diversity, genes to exchange on chromosomes, and expression of wild-type viral genomes.

 



 
Evolution

Evolution

Evolution (W)

Further information: RNA world hypothesis

DNA contains the genetic information that allows all forms of life to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material. RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes. This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes. However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution. Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old, but these claims are controversial.

Building blocks of DNA (adenine, guanine, and related organic molecules) may have been formed extraterrestrially in outer space. Complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have also been formed in the laboratory under conditions mimicking those found in outer space, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar cosmic dust and gas clouds.

 



 
Uses in technology

Genetic engineering

Genetic engineering (W)

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector. The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research, or be grown in agriculture.

 

 



DNA profiling

DNA profiling (W)

Further information: DNA profiling

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is formally termed DNA profiling, also called DNA fingerprinting. In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA. However, identification can be complicated if the scene is contaminated with DNA from several people. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys, and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.

The development of forensic science and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defense to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime.

DNA profiling is also used successfully to positively identify victims of mass casualty incidents, bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.

DNA profiling is also used in DNA paternity testing to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal DNA sequencing methods happen after birth, but there are new methods to test paternity while a mother is still pregnant.

 



DNA enzymes or catalytic DNA

DNA enzymes or catalytic DNA (W)

Further information: Deoxyribozyme

Deoxyribozymes, also called DNAzymes or catalytic DNA, were first discovered in 1994. They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, and etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction. The most extensively studied class of DNAzymes is RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific), the CA1-3 DNAzymes (copper-specific), the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific). The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in cells.

 



Bioinformatics

Bioinformatics (W)

Further information: Bioinformatics

Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning, and database theory. String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides. The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function. Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally. Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

 



DNA nanotechnology

DNA nanotechnology (W)

Further information: DNA nanotechnology

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties. DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra. Nanomechanical devices and algorithmic self-assembly have also been demonstrated, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.

 

The DNA structure at left (schematic shown) will self-assemble into the structure visualized by atomic force microscopy at right. DNA nanotechnology is the field that seeks to design nanoscale structures using the molecular recognition properties of DNA molecules. Image from Strong, 2004.

 



History and anthropology

History and anthropology (W)

Further information: Phylogenetics and Genetic genealogy

Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny. This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology.

 



Information storage

Information storage (W)

DNA as a storage device for information has enormous potential since it has much higher storage density compared to electronic devices. However, high costs, extremely slow read and write times (memory latency), and insufficient reliability has prevented its practical use.

 



 
History

History

History (W)



James Watson and Francis Crick (right), co-originators of the double-helix model, with Maclyn McCarty (left)
 
   
Further information: History of molecular biology

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein". In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases.

In 1909, Phoebus Levene identified the base, sugar, and phosphate nucleotide unit of the RNA (then named "yeast nucleic acid"). In 1929, Levene identified deoxyribose sugar in "thymus nucleic acid" (DNA). Levene sugested that DNA consisted of a string of four nucleotide units linked together through the phosphate groups ("tetranucleotide hypothesis"). Levene thought the chain was short and the bases repeated in a fixed order. In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template". In 1928, Frederick Griffith in his experiment discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. This system provided the first clear suggestion that DNA carries genetic information.

In 1933, while studying virgin sea urchin eggs, Jean Brachet suggested that DNA is found in the cell nucleus and that RNA is present exclusively in the cytoplasm. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH.

In 1937, William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.

In 1943, Oswald Avery, along with co-workers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle, supporting Griffith's suggestion (Avery–MacLeod–McCarty experiment). DNA's role in heredity was confirmed in 1952 when Alfred Hershey and Martha Chase in the Hershey–Chase experiment showed that DNA is the genetic material of the enterobacteria phage T2.

Late in 1951, Francis Crick started working with James Watson at the Cavendish Laboratory within the University of Cambridge. In February 1953, Linus Pauling and Robert Corey proposed a model for nucleic acids containing three intertwined chains, with the phosphates near the axis, and the bases on the outside. In May 1952, Raymond Gosling a graduate student working under the supervision of Rosalind Franklin took an X-ray diffraction image, labeled as "Photo 51", at high hydration levels of DNA. This photo was given to Watson and Crick by Maurice Wilkins and was critical to their obtaining the correct structure of DNA. Franklin told Crick and Watson that the backbones had to be on the outside. Before then, Linus Pauling, and Watson and Crick, had erroneous models with the chains inside and the bases pointing outwards. Her identification of the space group for DNA crystals revealed to Crick that the two DNA strands were antiparallel.

In February 1953, Watson and Crick completed their model, which is now accepted as the first correct model of the double-helix of DNA. On 28 February 1953 Crick interrupted patrons' lunchtime at The Eagle pub in Cambridge to announce that he and Watson had "discovered the secret of life".

In the 25 April 1953 issue of the journal Nature, were published a series of five articles giving the Watson and Crick double-helix structure DNA, and evidence supporting it. The structure was reported in a letter titled "MOLECULAR STRUCTURE OF NUCLEIC ACIDS A Structure for Deoxyribose Nucleic Acid", in which they said, "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." Followed by a letter from Franklin and Gosling, which was the first publication of their own X-ray diffraction data, and of their original analysis method. Then followed a letter by Wilkins, and two of his colleagues, which contained an analysis of in vivo B-DNA X-ray patterns, and supported the presence in vivo of the Watson and Crick structure.

In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.

In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson–Stahl experiment. Further work by Crick and co-workers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley, and Marshall Warren Nirenberg to decipher the genetic code. These findings represent the birth of molecular biology.

 



 
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