DNA polymerase
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226005647
2008-07-16T12:15:56Z
91.55.211.242
/* Eukaryotic DNA polymerases */
[[image:DNA_polymerase.png|thumb|3D structure of the DNA-binding [[helix-hairpin-helix]] motifs in human DNA polymerase beta]]
A '''DNA [[polymerase]]''' is an [[enzyme]] that assists in [[DNA replication]]. Such enzymes [[catalyze]] the [[polymerization]] of [[deoxyribonucleotide]]s alongside a [[DNA]] strand, which they "read" and use as a [[template]]. The newly-polymerized molecule is complementary to the template strand and identical to the template's partner strand.
DNA polymerase is considered to be a [[holoenzyme]] since it requires a [[magnesium]] ion as a co-factor to function properly. In the absence of the magnesium ion, it is referred to as an [[apoenzyme]].
DNA-Polymerase initiates DNA replication by binding to a piece of single-stranded DNA.
==Function==
[[Image:DNA_polymerase.svg|thumb|200px|right|DNA polymerase with proofreading ability.]]
DNA polymerase can add free nucleotides to only the 3’ end of the newly-forming strand. This results in elongation of the new strand in a [[5'-3']] direction. No known DNA polymerase is able to begin a new chain (''de novo''). DNA polymerase can add a nucleotide onto only a preexisting 3'-[[hydroxide|OH group]], and, therefore, needs a [[primer (molecular biology)|primer]] at which it can add the first nucleotide. Primers consist of [[RNA]] and DNA bases with the first two bases always being RNA, and are synthesized by another enzyme called [[primase]]. An enzyme known as a [[helicase]] is required to unwind DNA from a double-strand structure to a single-strand structure to facilitate replication of each strand consistent with the [[semiconservative]] model of DNA replication.
Error correction is a property of some, but not all, DNA polymerases. This process corrects mistakes in newly-synthesized DNA. When an incorrect base pair is recognized, DNA polymerase reverses its direction by one base pair of DNA. The 3'->5' [[exonuclease]] activity of the enzyme allows the incorrect base pair to be excised (this activity is known as ''proofreading''). Following base excision, the polymerase can re-insert the correct base and replication can continue.
==Variation across species==
DNA polymerases have highly-conserved structure, which means that their overall catalytic subunits vary, on a whole, very little from species to species. Conserved structures usually indicate important, irreplicable functions of the cell, the maintenance of which provides evolutionary advantages.
Some viruses also encode special DNA polymerases that may selectively replicate viral DNA through a variety of mechanisms. [[Retroviruses]] encode an unusual DNA polymerase called [[reverse transcriptase]], which is an RNA-dependent DNA polymerase (RdDp). It polymerizes DNA from a template of [[RNA]].
==DNA polymerase families==
Based on sequence homology, DNA polymerases can be further subdivided into seven different families: A, B, C, D, X, Y, and RT.
===Family A===
Family A polymerases contain both replicative and repair polymerases. Replicative members from this family include the extensively-studied [[T7 DNA polymerase]], as well as the eukaryotic mitochondrial DNA Polymerase γ. Among the repair polymerases are ''E. coli'' DNA pol I, ''[[Thermus aquaticus]]'' pol I, and ''[[Bacillus stearothermophilus]]'' pol I. These repair polymerases are involved in excision repair and processing of [[Okazaki fragment]]s generated during lagging strand synthesis.
===Family B===
Family B polymerases mostly contain replicative polymerases and include the major eukaryotic DNA polymerases α, δ, ε, (see [[Greek letters used in mathematics]]) and also DNA polymerase ζ. Family B also includes DNA polymerases encoded by some bacteria and bacteriophages, of which the best-characterized are from T4, Phi29, and RB69 bacteriophages. These enzymes are involved in both leading and lagging strand synthesis. A hallmark of the B family of polymerases is remarkable accuracy during replication; and many have strong 3'-5' exonuclease activity (except DNA polymerase α and ζ, which have no proofreading activity).
===Family C===
Family C polymerases are the primary bacterial chromosomal replicative enzymes. DNA Polymerase III alpha subunit from ''E. coli'' possesses no known nuclease activity. A separate subunit, the epsilon subunit, possesses the 3'-5' exonuclease activity used for editing during chromosomal replication.
===Family D===
Family D polymerases are still not very well characterized. All known examples are found in the [[Euryarchaeota]] subdomain of Archaea and are thought to be replicative polymerases.
===Families X===
Family X contains the well-known eukaryotic polymerase pol β, as well as other eukaryotic polymerases such as pol σ, pol λ, pol μ, and terminal deoxynucleotidyl transferase (TdT). Pol β is required for short-patch [[base excision repair]], a DNA repair pathway that is essential for repairing abasic sites. Pol λ and Pol μ are involved in [[non-homologous end-joining]], a mechanism for rejoining DNA double-strand breaks. TdT is expressed only in lymphoid tissue, and adds "n nucleotides" to double-strand breaks formed during [[V(D)J recombination]] to promote immunological diversity. The yeast ''[[Saccharomyces cerevisiae]]'' has only one Pol X polymerase, [[Pol4]], which is involved in [[non-homologous end-joining]].
===Families Y===
The Y-family polymerases differ from others in having a low fidelity on undamaged templates and in their ability to replicate through damaged DNA. Members of this family are hence called translesion synthesis (TLS) polymerases. Depending on the lesion, TLS polymerases can bypass the damage in an error-free or error-prone fashion, the latter resulting in elevated mutagenesis. [[Xeroderma pigmentosum]] variant (XPV) patients for instance have mutations in the gene encoding Pol η (eta), which is error-free for UV-lesions. In XPV patients, alternative error-prone polymerases, e.g., Polζ (zeta) (polymerase ζ is a B Family polymerase), are thought to be involved in mistakes that result in the cancer predisposition of these patients. Other members in humans are Pol ι (iota), Pol κ (kappa), and Rev1 (terminal deoxycytidyl transferase). In E.coli, two TLS polymerases, Pol IV (DINB) and PolV (UmuD'<sub>2</sub>C), are known.
===Family RT===
The reverse transcriptase family contains examples from both retroviruses and eukaryotic polymerases. The eukaryotic polymerases are usually restricted to [[telomerase]]s. These polymerases use an RNA template to synthesize the DNA strand.
==Prokaryotic DNA polymerases==
Bacteria have 5 known DNA polymerases:
*'''[[DNA polymerase I|Pol I]]''': implicated in DNA repair; has both 5'->3'([[Polymerase]]) activity and 3'->5' ([[Proofreading]]) exonuclease activity.
*'''[[DNA polymerase II|Pol II]]''': involved in replication of damaged DNA; has 3'->5' exonuclease activity.
*'''[[DNA polymerase III holoenzyme|Pol III]]''': the main polymerase in bacteria (elongates in DNA replication); has 3'->5' exonuclease proofreading ability.
*'''[[Pol IV]]''': a Y-family DNA polymerase.
*'''[[Pol V]]''': a Y-family DNA polymerase; participates in bypassing DNA damage.
==Eukaryotic DNA polymerases==
Eukaryotes have at least 15 DNA Polymerases:<ref>{{cite journal| author=I. Hubscher, U.; Maga, G.; Spadari, S. | date=2002 | title=Eukaryotic DNA polymerases| journal = Annual Review of Biochemistry | volume = 71| page= 133-63 | pmid=12045093 | doi = 10.1146/annurev.biochem.71.090501.150041| pages=133}}</ref>
*'''Pol α''' (synonyms are DNA primase, '''RNA''' polymerase): acts as a primase (synthesizing an RNA primer), and then as a DNA Pol elongating that primer with DNA nucleotides. After around 20 nucleotides<ref>J. M. Berg; J. L. Tymoczko; L. Stryer "Biochemie", Springer, Heidelberg/Berlin 2003</ref> elongation is taken over by Pol δ (on the lagging strand) and ε (on the leading strand).
*'''Pol β''': Implicated in repairing DNA, in base excision repair and gap-filling synthesis.
*'''Pol γ''': Replicates [[mitochondrial DNA]].
*'''Pol δ''': Highly processive and has proofreading 3'->5' exonuclease activity. Thought to be the main polymerase involved in lagging strand synthesis, though there is still debate about its role<ref>{{cite journal| author=Scott D McCulloch; Thomas A Kunkel | date=01/2008 | title=The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases | journal = Cell Research | volume = 18| page= 148-161 | pmid=18166979 | doi = 10.1038/cr.2008.4| pages=148}}</ref>.
*'''Pol ε''': Also highly processive and has proofreading 3'->5' exonuclease activity. Highly related to pol δ, and thought to be the main polymerase involved in leading strand synthesis<ref>{{cite journal| author=Pursell, Z.F. et al. | date=2007 | title= Yeast DNA Polymerase ε Participates in Leading-Strand DNA Replication | journal=Science | volume= 317 | page= 127-130 | pmid=17615360 | doi=10.1126/science.1144067| pages=127}}</ref>, though there is again still debate about its role<ref>{{cite journal| author=Scott D McCulloch; Thomas A Kunkel | date=01/2008 | title=The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases | journal = Cell Research | volume = 18| page= 148-161 | pmid=18166979 | doi = 10.1038/cr.2008.4| pages=148}}</ref>.
*'''[[DNA polymerase eta|η]]''', '''ι''', '''κ''', and '''Rev1''' are Y-family DNA polymerases and '''Pol ζ''' is a B-family DNA polymerase. These polymerases are involved in the bypass of DNA damage.<ref>{{cite journal| author=I. Prakash, S.; Johnson, R. E.; Prakash, L. | date=2005 | title= Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function | journal= Annual Review of Biochemistry | volume= 74 | page= 317-53| doi=10.1146/annurev.biochem.74.082803.133250 | pmid=15952890| pages=317}}</ref>
*There are also other eukaryotic polymerases known, which are not as well characterized: '''θ''', '''λ''', '''φ''', '''σ''', and '''μ'''. There are also others, but the nomenclature has become quite jumbled.
None of the eukariotic polymerases can remove primers (5'->3' exonuclease activity); that function is carried out by other enzymes. Only the polymerases that deal with the elongation (γ, δ and ε) have proofreading ability (3'->5' exonuclease). nuclease is a great advocate for DNA replication.
==See also==
*[[Polymerase chain reaction]]
*[[RNA polymerase]]
== References ==
===Citations===
<references/>
==External links==
*{{cite journal |author=Burgers P, Koonin E, Bruford E et al. |title=Eukaryotic DNA polymerases: proposal for a revised nomenclature |journal=J. Biol. Chem. |volume=276 |issue=47 |pages=43487–90 |year=2001 |pmid=11579108 |doi= 10.1074/jbc.R100056200}}
*{{PDB Molecule of the Month|pdb3_1}}
*[http://researchnews.osu.edu/archive/repprot.htm Unusual repair mechanism in DNA polymerase lambda], [[Ohio State University]], July 25, 2006.
* {{MeshName|DNA+polymerases}}
* {{EC number|2.7.7.7}}
*[http://www.wehi.edu.au/education/wehi-tv/dna/replication.html A great animation of DNA Polymerase from WEHI]
{{Polymerases}}
[[Category:EC 2.7.7]]
[[Category:DNA replication]]
[[Category:DNA]]
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