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DNA polymerase

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 deoxyribonucleotides 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.

FunctionEdit

DNA polymerase can only add free nucleotides to 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). They can only add a nucleotide onto a preexisting 3'-OH group. For this reason, DNA polymerase needs a 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 speciesEdit

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 evolutionary advantages.

Some viruses also encode special DNA polymerases which 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 familiesEdit

Based on sequence homology, DNA polymerases can be further subdivided into seven different families A, B, C, D, X, Y, and RT.

Family AEdit

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 fragments generated during lagging strand synthesis.

Family BEdit

Family B polymerases mostly contain replicative polymerases and include the major eukaryotic DNA polymerases α, δ, ε, 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 CEdit

Family C polymerases are the primary bacterial chromosomal replicative enzymes and thus have polymerase and 3'-5' exonuclease activity.

Family DEdit

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 XEdit

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 only expressed in lymphoid tissue and adds "n nucleotides" to double-strand breaks formed during V(D)J recombination to promote immunological diversity.

Families YEdit

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 sythesis (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 which 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 (UMUC), are known.

Family RTEdit

Finally, the reverse transcriptase family contain examples both from retroviruses and eukaryotic polymerases. The eukaryotic polymerases are usually restricted to telomerases. These polymerases use a RNA template to synthesize the DNA strand.

Prokaryotic DNA polymerasesEdit

Bacteria have 5 known DNA polymerases:

  • Pol I: implicated in DNA repair; has both 5'->3'(Nick translation) and 3'->5' (Proofreading) exonuclease activity.
  • Pol II: involved in replication of damaged DNA; has both 5'->3'chain extension ability and 3'->5' exonuclease activity.
  • 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 polymerasesEdit

Eukaryotes have at least 15 DNA Polymerases[1]:

  • Pol α: acts as a primase (synthesizing a RNA primer), and then as a DNA Pol elongating that primer with DNA nucleotides. After around 20 nucleotides[2] elongation is taken over by Pol δ and ε.
  • Pol β: is implicated in repairing DNA.
  • Pol γ: replicates mitochondrial DNA.
  • Pol δ: is the main polymerase in eukaryotes, it is highly processive and has 3'->5' exonuclease activity.
  • Pol ε: may substitute for Pol δ in lagging strand synthesis, however the exact role is uncertain.
  • 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.[3]
  • 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. See the External Links or do a quick search of PubMed to get the most up-to-date information.

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).

See alsoEdit

References Edit

CitationsEdit

  1. I. Hubscher, U.; Maga, G.; Spadari, S. (2002) Eukaryotic DNA polymerases. Annual Review of Biochemistry 71, 133-63.
  2. J. M. Berg; J. L. Tymoczko; L. Stryer "Biochemie", Springer, Heidelberg/Berlin 2003
  3. I. Prakash, S.; Johnson, R. E.; Prakash, L. (2005) Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annual Review of Biochemistry 74, 317-53.

External linksEdit


ca:DNA-polimerasa

de:DNA-Polymerase es:ADN polimerasa fa:دی‌ان‌ای-پلی‌مراز fr:ADN polymérase he:DNA פולימראז lt:DNR polimerazė nl:DNA-polymerasesk:DNA-polymeráza sr:ДНК полимераза sv:DNA-polymeras vi:DNA polymerase zh:DNA聚合酶

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