Proteopedia

DNA: Difference between revisions

← Older edit
Eran Hodis (talk | contribs)
7,087 edits
No edit summary
Eric Martz (talk | contribs)
ConfirmAccount, Editor, Tester, Administrators
27,351 edits
No edit summary
 
(190 intermediate revisions by 14 users not shown)
Line 1: Line 1:
[[Image:MotM B-DNA.gif |left |100px]]
{{BAMBED
{{Applet
|DATE=August 20, 2011
|PDB= 1bna |SIZE=320|SCENE=DNA/Initial/1|CAPTION= B-helix DNA from PDB entry <scene name='DNA/Initial/1'>1bna</scene>
|OLDID=1286497
|BAMBEDDOI=10.1002/bmb.20566
}}
}}
Each of the cells in your body carries about 1.5 gigabytes of genetic information, stored as [[DNA]], an amount of information that would fill two CD ROMs or a small hard disk drive. Surprisingly, when placed in an appropriate egg cell, this amount of information is enough to build an entire living, breathing, thinking human being. Through the efforts of the international human genome sequencing projects, you can now read this information. Along with most of biological research community, you can marvel at the complexity of this information and try to understand what it means. At the same time, you can wonder at the simplicity of this information when compared to the intricacy of the human body.
<StructureSection load='B-DNA.pdb' size='450' side='right' scene='DNA/B-dna/7' caption='The double-helical structure of B-DNA, shown as ball-and-stick (colored by element {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_H}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}} {{Template:ColorKey_Element_P}}) with the helical conformation of the sugar-phosphate shown as orange ribbon, and the planes of the nucleobases (drag down in the viewer to see them) in orange as well.'>


DNA stands for deoxyribonucleic acid. Attached to a long backbone made up of sugars and phosphate groups, is a long polymer of nucleotides (adenine, thymine, guanine, and cytosine). DNA stores information via its sequence of nucleotides.  Different DNA molecules will share the same backbone, but will have different sequences of nucleotides encoding different genetic information. The two strands of DNA are complementary to each other, and interact via hydrogen bonds between complementary nucleotides (adenine with thymine and guanine with cytosine).
'''Deoxyribonucleic acid''' or '''DNA''' is a molecule which is the carrier of genetic information in nearly all the living organisms. It contains the biological instructions for the development, survival and reproduction of organisms.
DNA is found in the nucleus of a cell where it is packaged into a compact form called a chromosome with the help of several proteins known as histones. It is also found in cell structures called mitochondria. However in case of prokaryotes DNA is not enclosed in a nucleus or a membrane but is present in the cytoplasm. The DNA in prokaryotes in generally circular and supercoiled without any histones. DNA stores genetic information as a sequence of nucleotides in special regions known as genes which are used to make proteins. The expression of genetic information into proteins is a two-stage process wherein the sequence of nucleotides in DNA is converted to a molecule called Ribonucleic acid or [[RNA]] by a process called [[transcription]]. RNA is used to make proteins by another process called [[translation]]. The human genome contains nearly 3 · 10<sup>9</sup> bases with around 20,000 genes on 23 chromosomes. <ref name='gene'>http://www.genome.gov/25520880 </ref>
   
DNA was first discovered by the German biochemist Frederich Miescher in the year 1869.<ref>PMID: 17901982</ref> Based on the works of Erwin Chargaff, James Watson, Francis Crick, Maurice Wilkins and Rosalind Franklin, the structure of DNA was discovered in the year 1953. The structure of DNA is a <scene name='DNA/B-dna/15'>double helix</scene>: two complementary strands of polynucleotides that run in opposite directions and are held together by hydrogen bonds between them.<ref name='structure'>A Structure for Deoxyribose Nucleic Acid
Watson J.D. and Crick F.H.C.
Nature 171, 737-738 (1953)</ref> This structure helps the DNA replicate itself during cell division and also for a single strand to serve as template during transcription. <ref name='gene'>http://www.genome.gov/25520880 </ref>


<scene name='DNA/B-dna/7'>Restore View</scene>
== Features of a DNA Molecule ==
=== Double Helix ===
<scene name='User:Adithya_Sagar/Sandbox_DNA/B-dna/4'>DNA</scene> consists of two polynucleotide chains, <scene name='DNA/B-dna/16'>twisted around each other to form a double helix</scene>. The <scene name='10/100853/Nucleotide/2'>nucleotide</scene> in DNA is composed of a <scene name='10/100853/Phosphate/3'>phosphate</scene> bonded to the 5' of <scene name='10/100853/Deoxyribose/2'>D-2'-deoxyribose</scene> which is connected by a beta-glycosidic bond to a purine or a pyrimidine <scene name='10/100853/Base/2'>base</scene>. The <scene name='10/100853/Ribose_pucker/3'>ring pucker</scene> of ribose is a main determinant of which of the [[Forms of DNA]] is present. In this scene, which shows B DNA, the 2' carbon is out of the plane of the other members of the five membered ring.  In <scene name='10/100853/3_endo_a_dna/2'>A form DNA</scene>, the 3' carbon is out of the plane of the ribose ring.
The four types of bases are the two double-ringed purine base <scene name='10/100853/B-dna/38'>Adenine (A)</scene> and <scene name='10/100853/B-dna/39'>Guanine (G)</scene> and the two single-ringed pyrimidine bases <scene name='10/100853/B-dna/40'>Thymine (T)</scene> and <scene name='10/100853/B-dna/41'>Cytosine (C)</scene>. Hydrogen atoms on some nitrogen and oxygen atom can undergo tautomeric shifts. The nitrogen atoms that are involved in forming tautomer appear as amino or imino groups and the oxygen atoms are either in keto or enol forms. Using an isolate thymine to illustrate the <scene name='DNA/Thymine_enol/1'>imino/enol tautomer</scene> and the <scene name='DNA/Thymine_keto/3'>amino/keto tautomer</scene>. There is a preference for the amino and keto forms which is very crucial for the biological functioning of DNA as it provides a <scene name='10/100853/Amino-glycosidic/2'>ring nitrogen capable of forming a glycosidic bond</scene> with the deoxyribose and it leads to the specificity of hydrogen bonding in base pairing and thus complementarity of the chains.<ref name='Watson'> Watson, James D, Nancy H. Hopkins, Jeffrey W. Roberts, Joan Argetsinger Steitz, Alan M.Weiner ''Molecular Biology of Gene'' (4th ed.). The Benjamin/Cummings Publishing Company Inc.pp. 239-249. ISBN 0-8053-9612-8</ref> The imino nitrogen can only serve as a donating atom in hydrogen bonding, but the amino nitrogen can also serve as a receiving atom. Each nucleotide in a DNA chain is linked to another via <scene name='10/100853/Diester/3'>3',5' phosphodiester bond</scene>. There are four nucleotides in DNA.  The sugar-phosphate backbone of the DNA is very regular owing to the phosphodiester linkage whereas the ordering of bases is highly irregular.<ref name='Watson'> Watson, James D, Nancy H. Hopkins, Jeffrey W. Roberts, Joan Argetsinger Steitz, Alan M.Weiner ''Molecular Biology of Gene'' (4th ed.). The Benjamin/Cummings Publishing Company Inc.pp. 239-249. ISBN 0-8053-9612-8</ref>
<scene name='DNA/B-dna/17'>Restore View</scene>
{| class="wikitable" align= "center''
|-
|}
{{Template:Button Toggle NucleicDrumsColorScheme}}
{{Template:ColorKey Bases DNA}}
{| class="wikitable" align= "center''
|-
|}
{{Template:Button Toggle PurinePyrimidineDrumsColorScheme}}
{{Template:ColorKey Purines Pyrimidines}}


== Read-Only Memory ==
=== Complementary Bases ===
DNA is read-only memory, archived safely inside cells. Genetic information is stored in an orderly manner in strands of DNA. DNA is composed of a long linear strand of millions of nucleotides, and is most often found paired with a partner strand, which wrap around one another in the familiar double helix. The code is quite easy to read: you simply step down the strand of DNA one nucleotide at a time and read off the bases: A, T, C or G. This is exactly what your cells do: they scan down a messenger RNA (copied from the DNA), and use ribosomes to build proteins based on the code that is read. This is also how researchers determine the sequence of a DNA strand: they clip off one nucleotide at a time to see what it is.


== Your Inheritance ==
The two chains in a DNA are joined by hydrogen bonds between specific bases. Adenine forms base pairs with thymine and guanine with cytosine. This specific base pairing between <scene name='User:Adithya_Sagar/Workbench_newDNA/B-dna/14'>Adenine-Thymine</scene> and <scene name='User:Adithya_Sagar/Workbench_newDNA/B-dna/15'>Guanine-Cytosine</scene> is known as the Watson-Crick base pairing.  The specificity of hydrogen bonding between bases leads to complementarity in the sequence of nucleotides in the two chains.<ref name='structure'>A Structure for Deoxyribose Nucleic Acid
Watson J.D. and Crick F.H.C.
Nature 171, 737-738 (1953)</ref> Thus in a strand of DNA the content of adenine is equal to that of thymine  and the guanine content is equal to the cytosine content.  In general DNA with higher GC content is more stable than the one with higher AT content owing to the stabilization due to [[base stacking]] interactions.


Your genetic information, inherited from your parents, is your most precious possession. It guided the construction of your body in the first nine months of your life and it continues to control all of the basic functions of living. Each of your cells is constantly using this information, asking questions about how to control blood sugar levels and body temperature, how to digest different foods and how to deal with new environmental challenges, and thousands of other important questions. The answers are held in the DNA. Hundreds of different proteins are built to interact with this information: to read it and use it to build new proteins, to copy it when the cell divides, to store and protect it when it is not actively being used, and to repair the information when it becomes corrupted by chemicals or radiation.
=== DNA denaturation and renaturation ===


== A Central Icon ==
A DNA double strand can be separated into two single strands by breaking the hydrogen bonds between them. This is known as DNA denaturation.  Thermal energy provided by heating can be used to melt or denature DNA. Molecules with rich GC content are more stable and thus denature at higher temperatures compared to the ones with higher AT content. The melting temperature is defined as the temperature at which half the DNA strands are in double helical state and half are in random coil state.<ref>PMID: 9465037</ref> The denatured DNA single strands have an ability to renature and form double stranded DNA again.


DNA is arguably one of the most beautiful molecules in living cells. Its graceful helix is pleasing to the eye. DNA is also one of the most familiar molecules, the central icon of molecular biology, easily recognized by everyone. To some, it may carry a negative connotation, being a pervasive symbol for activists against genetically engineered produce. To others, it may bring to mind advances in forensics such as the DNA fingerprinting used in many recent high-profile trials. Some may have seen it in science fiction, modified to build dinosaurs or store cryptic messages from aliens. To all it is a pervasive symbol of our growing understanding of the human body and our close kinship with the rest of the biosphere, and the moral and ethical issues that must be addressed in the face of that knowledge.
=== Grooves ===
In a <scene name='DNA/Bdnasf/1'>DNA double helix</scene> the <scene name='DNA/Angled_gylcosidic/5'>beta-glycosyl bonds</scene> of bases which are paired <scene name='DNA/Angled_gylcosidic/7'>do not lie opposite</scene> to each other but are positioned at an angle.  


== Molecular Information ==
[[Image:DNA grooves.png|200px]]
[[Image:MotM Information.gif |right |thumb|500px]]
DNA is perfect for the storage and readout of information. It is laden with information. Every surface and edge of the molecule carries information. The basic mechanism by which DNA stores and transmits genetic information was discovered in the 1950's by Watson and Crick. This basic information is stored in the way that the bases match one another on opposite sides of the double helix--adenine with thymine, guanine with cytosine--forming a set of complementary hydrogen bonds. These are shown in the diagram with red arrows.
Additional 'extragenetic' information is read from the surfaces that are left exposed in the double helix. In the major groove (the wider of the two grooves in the structure on the left), the different base pairs have a characteristic pattern of chemical groups that carry information, shown by green arrows in the close-up diagrams on the right. These include hydrogen bond donors (D) and acceptors (A) as well as a site with a large, bulky group in adenine-thymine base pairs (large asterisk) or a small group in guanine-cytosine base pairs (small asterisk). In the minor groove, there is a different arrangement of chemical groups that carry additional information, indicated with blue arrows in the diagram on the right and the blue letters in the structure on the left. As revealed in hundreds of structures in the PDB, this extragenetic information is used by proteins to read the genetic code in DNA without unwinding the double helix. It is also targeted by a number of toxins and drugs that attack DNA.


== Variations on a Theme ==
This results in unequally spaced sugar-phosphate backbones and gives rise to <scene name='10/100853/Grooves/2'>two grooves</scene>: the
[[Image:MotM ABZ.gif |left |thumb|250px|Left: A-DNA from [[1ana]], Center: B-helix from [[1bna]], Right: Z-DNA from [[2dcg]]. Idealized models are shown in red/white/green with superimposed examples from crystal structures in white/red/yellow/blue.]]
<scene name='DNA/Major_groove/2'>major groove</scene> and the <scene name='DNA/Major_groove/7'>minor groove</scene> of different width and depth. The <scene name='DNA/Major_groove/8'>oxygen atoms of the furanose rings</scene> are on the surface of the minor groove, and the major groove is on the opposite side. The floor or surface of major groove is filled with the <scene name='DNA/Major_floor/2'>atoms of the bases</scene>. The larger size of major groove allows for the binding of DNA specific  proteins.<ref name="Saenger"> Saenger, Wolfram (1984). ''Principles of Nucleic Acid Structure '' (1st ed). Springer-Verlag. pp. 398. ISBN 0-12-645750-6.</ref><ref name='Watson'> Watson, James D, Nancy H. Hopkins, Jeffrey W. Roberts, Joan Argetsinger Steitz, Alan M.Weiner ''Molecular Biology of Gene'' (4th ed.). The Benjamin/Cummings Publishing Company Inc.pp. 239-249. ISBN 0-8053-9612-8</ref>
DNA adopts the familiar smooth double helix, termed a B-helix, under the typical conditions found in living cells. An example is shown in the center in the adjacent image, exemplified by the crystal structure [[1bna]], shown at the top superimposed over the idealized version of the B-helix. Under other conditions, however, DNA can form other structures, as revealed in two early crystal structures: [[1ana]] on the left and [[2dcg]] on the right. The one on the left, with tipped bases and a deep major groove, is termed A-DNA. It is formed under dehydrating conditions. Also, RNA most often shows this form, because its extra hydroxyl group on the sugar gets in the way, making the B-form unstable (look, for instance, at the A-helical structure of transfer RNA shown in a previous Molecule of the Month). The form on the right, which winds in the opposite direction from A-DNA and B- DNA, is termed Z-DNA. It is found under high salt conditions and requires a special type of base sequence, with many alternating cytosine-guanine and guanine-cytosine base pairs.


{{Clear}}
== Biological Functions ==
''Sources:''<ref name='Rawn' > Rawn,David J. "Biochemistry"(1st ed.) Harper&Row,Publishers, Inc.pp. 1024-1050. ISBN-0-06045335-4</ref>


== Exploring the Structure ==
=== Replication===
<applet load='1bna' size='400' frame='true' align='left' caption='Small piece of DNA' />
DNA undergoes what is known as semi conservative mode of replication wherein the daughter DNA contains one DNA strand of the parent. The replication proceeds through the unwinding of double helix followed by synthesis primers from where the replication begins. An enzyme DNA polymerase synthesizes complementary strands to each parent strand from 5'-3' direction.


We often think of DNA as a perfect, smooth double helix. In reality, DNA has a lot of local structure. The small piece of DNA shown here, <scene name='DNA/1bna/7'>1bna</scene>, shows some of the common variations. At the top, the helix is bent to the left, distorted by the way that the helices are packed into the crystal. At the bottom, two of the bases are strongly propeller twisted--they are not in one perfect plane. This improves the way that the bases stack on top of one another along each strand, stabilizing the whole double helix. As more and more structures of DNA are studied, it is becoming clear that DNA is a dynamic molecule, quite flexible on its own, which is bent, kinked, knotted and unknotted, unwound and rewound by the proteins that interact with it.
===Transcription and Translation===
The expression of genes into proteins and is a process involving two stages called transcription and translation. In the transcription stage a strand of DNA molecule serves as a template for the synthesis of an RNA molecule called messenger RNA. This messenger RNA is then translated into proteins on ribosomes.


{{Clear}}
==Forms of DNA==
For a comparison of the different forms of DNA, see [[forms of DNA]].


==Additional Information==
== History of DNA Structure ==


# [http://en.wikipedia.org/wiki/DNA DNA in Wikipedia]
The following summary is copied from an [http://atlas.molviz.org Atlas of Macromolecules] with permission:


== Acknowledgements ==
:Genes were shown to reside in DNA in 1944 (Avery et al.) and this became widely accepted after the 1952 experiments of Hershey and Chase. The double helical structure of the DNA was predicted by James Watson and Francis Crick in 1953 (Nobel Prize, 1962). Their prediction was based in part upon X-ray diffraction studies by Rosalind Franklin, to whom Watson and Maurice Wilkins gave inadequate credit<ref>Maddox, Brenda: ''Rosalind Franklin: Dark Lady of DNA'', HarperCollins, 2002</ref>. The predicted B-form double helix was not confirmed with atomic-resolution crystal structures until 1973, first by using dinucleotides of RNA (Rosenberg et al.). The first crystal structure containing more than a full turn of the double helix was not solved until 1980 ([[1bna]], 1981, 12 base pairs). The lag of more than a quarter century between prediction and empirical confirmation involved development of [[X-ray crystallography]] for macromolecules, and the need to produce a short, defined sequence of DNA for crystallization. This brief account is based upon a review by Berman, Gelbin, and Westbrook <ref>PMID: 9284453</ref>, where the references will be found.


*Content adapted with permission from David S. Goodsell's [http://mgl.scripps.edu/people/goodsell/pdb/pdb23/pdb23_1.html Molecule of the Month on DNA]
== DNA Models ==
 
The model of DNA used in the scenes in the present article is a theoretical model<ref>PMID: 8832384</ref> ([[Image:B-DNA.pdb]]), not available in the [[Protein Data Bank]]. The [[PDB file]] does not follow certain PDB format conventions:
* Bases are designated ADE, CYT, GUA, and THY instead of the standard DA, DC, DG and DT.
* The chains are not named. Typically they would be named A and B.
 
One chain contains residues numbered 1-12 in sequence CGCG AATT CGCG. The other chain contains residues numbered 13-24 with an identical (antiparallel) sequence.
 
Theoretical models typically represent idealized DNA conformation, whereas real DNA may have various irregularities including kinks and bends (see examples bound to the [[Lac repressor]]). There are plenty of empirical models for DNA, the first having become available in the 1970's and 80's (see [[#History of DNA Structure|above]]). In May, 2012, the [[Protein Data Bank]] contains nearly 4,000 entries containing DNA. Over 1,300 contain only DNA, while over 2,000 contain protein-DNA complexes. Over 100 entries contain protein, DNA and [[RNA]], and over 100 contain DNA/RNA hybrid molecules.
 
For more interactive visualizations of DNA, see [http://dna.molviz.org DNA.MolviZ.Org], a tutorial that is available in [http://biomodel.uah.es/model4/dna/ nine languages].
 
</StructureSection>
 
__NOTOC__
== See Also ==
===Proteopedia Articles===
*[[Forms of DNA]]
* Kinks vs. Bends in DNA are discussed in [[Lac repressor]].
* [[User:Karsten Theis/DNA bulges|DNA bulges]] occur when a nucleotide is inserted in one strand but not the other, causing an interruption in base pairing.
*[[1ply]]
*[[DNA Replication, Repair, and Recombination]] - Articles in Proteopedia concerning DNA Replication, Repair, and/or Recombination
*[[DNA Replication,Transcription and Translation]]
*[[Z-DNA]]
*[[tRNA|Transfer ribonucleic acid (tRNA)]]
* For additional information, see: [[Nucleic Acids]]
===External Resources===
* [http://dna.molviz.org DNA.MolviZ.Org], an interactive DNA Structure tutorial that is available in [http://biomodel.uah.es/model4/dna/ nine languages].
* [http://bioinformatics.org/molvis/atlas/atlas.htm#dnarna DNA / RNA Section of the Atlas of Macromolecules].
====Interpretation of X-Ray Diffraction by DNA====
* [http://www-tc.pbs.org/wgbh/nova/photo51/media/anatomy.swf Anatomy of Photo 51], Rosalind Franklin's diffraction pattern used by Watson & Crick in developing their model of the DNA double helix (at PBS.Org, US Public Broadcasting System).
* [http://www.dnalc.org/view/15014-Franklin-s-X-ray-diffraction-explanation-of-X-ray-pattern-.html Explanation of Franklin's X-Ray Diffraction Pattern] at Cold Spring Harbor Laboratory, USA.
* More technical: [http://homepages.ius.edu/kforinas/P105/PTE000140.pdf How Rosalind Franklin Discovered the Helical Structure of DNA: Experiments in Diffraction].
 
== References==
<references/>
 
[[Category:Featured in BAMBED]]
Retrieved from "https://proteopedia.openfox.io/w/DNA"