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. Image File history File links Download high resolution version (582x618, 48 KB) Image by uploader, created using SwissPDB viewer from PDB file: Source: Homo sapiens; expression system: Escherichia coli Authors: H. Pelletier; M. R. Sawaya Reference: Characterization of the DNA-binding helix-hairpin-helix motifs in human DNA polymerase beta... Image File history File links Download high resolution version (582x618, 48 KB) Image by uploader, created using SwissPDB viewer from PDB file: Source: Homo sapiens; expression system: Escherichia coli Authors: H. Pelletier; M. R. Sawaya Reference: Characterization of the DNA-binding helix-hairpin-helix motifs in human DNA polymerase beta... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... ITaq DNA polymerase A polymerase (EC 2. ... This article or section is in need of attention from an expert on the subject. ... A deoxyribonucleotide is the monomer, or single unit, of DNA, or deoxyribonucleic acid. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ...

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. In biochemistry, holoenzyme may refer either to the complete and operative form of an enzyme with multiple protein subunits or to the combination of an apoenzyme with its cofactor. ... General Name, Symbol, Number magnesium, Mg, 12 Chemical series alkaline earth metals Group, Period, Block 2, 3, s Appearance silvery white Atomic mass 24. ... An apoenzyme is an enzyme without its cofactor; that is, the protein molecule to which a coenzyme will bind to produce the holoenzyme. ...

DNA-Polymerase initiates DNA replication by binding to a piece of single-stranded DNA.

Function

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. A diagram of a furanose (sugar-ring) molecule with carbons labelled numerically Directionality, in molecular biology, refers to the end-to-end chemical orientation of a single strand of nucleic acid. ... Hydroxide is a polyatomic ion consisting of oxygen and hydrogen: OH− It has a charge of −1. ... A primer is a nucleic acid strand, or a related molecule that serves as a starting point for DNA replication. ... This article or section does not adequately cite its references or sources. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... DNA primase is a form of RNA polymerase and a product of the dnaG gene. ... This article or section does not adequately cite its references or sources. ... Semiconservative replication describes the method by which DNA is replicated in all known cells. ... This article or section is in need of attention from an expert on the subject. ...

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. Exonucleases are enzymes that cleave nucleotides one at a time from an end of a polynucleotide chain. ...

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, irreplacable functions of the cell, the maintenance of which provides 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. Stop editing pages god ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... Genera Alpharetrovirus Betaretrovirus Gammaretrovirus Deltaretrovirus Epsilonretrovirus Lentivirus Spumavirus A retrovirus is a virus which has a genome consisting of two identical plus sense RNA molecules. ... In biochemistry, a reverse transcriptase, also known as RNA-directed DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into double-stranded DNA. Normal transcription involves the synthesis of RNA from DNA, hence reverse transcription is the reverse of this, as it synthesises DNA from RNA. Reverse... This article or section does not adequately cite its references or sources. ...

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 fragments generated during lagging strand synthesis. Binomial name Thermophilus aquaticus Brock & Freeze, 1969 Thermophilus aquaticus is a species of bacterium that can tolerate high temperatures; it is the source of the heat-resistant enzyme Taq DNA Polymerase, one of the most important enzymes in molecular biology because of its use in the polymerase chain reaction. ... Bacillus stearothermophilus is a rod-shaped, Gram-positive bacteria and a member of the division Firmicutes. ... śś¼Wiki markup: {{}} | [] [[]] [[Category:]] #REDIRECT [[]] Cite error 4; Invalid <ref> tag; refs with no name must have content • (templates) Okazaki fragment is a relatively short fragment of DNA (with an RNA primer at the 5 terminus) created on the lagging strand during DNA replication. ...

Family B

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 C

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

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. Classes Halobacteria Methanobacteria Methanococci Methanomicrobia Methanosarcinae Methanopyri Archaeoglobi Thermoplasmata Thermococci The Euryarchaeota are a major group of Archaea. ...

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 only expressed 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. This article needs to be cleaned up to conform to a higher standard of quality. ... Non-homologous end joining (NHEJ) is one pathway that can be used to repair double-stranded DNA breaks. ... V(D)J recombination is a mechanism of DNA recombination used by humans and other vertebrates for immunological protection against attacks by bacterial, viral, and parasitic invaders. ... Binomial name Saccharomyces cerevisiae Meyen ex E.C. Hansen Saccharomyces cerevisiae is a species of budding yeast. ... Non-homologous end joining (NHEJ) is one pathway that can be used to repair double-stranded DNA breaks. ...

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 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. This article or section does not adequately cite its references or sources. ...

Family RT

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. Telomerase is an enzyme that adds specific DNA sequence repeats (TTAGGG in all vertebrates) to the 3 (three prime) end of DNA strands in the telomere regions, which are found at the ends of eukaryotic chromosomes. ...

Prokaryotic DNA polymerases

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.

DNA polymerase I is an enzyme that mediates the process of DNA replication in prokaryotes. ... Nick translation is a tagging technique from molecular biology in which endonucleases are used to remove some of the nucleotides of a DNA sequence. ... Proofreading means reading a proof copy of a text in order to detect and correct any errors. ... DNA polymerase II (also known as DNA Pol II or Pol II) is a prokaryotic DNA polymerase most likely involved in DNA repair. ... DNA polymerase III holoenzyme or Pol III is a holoenzyme that aids in DNA replication. ...

Eukaryotic DNA polymerases

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). // Mitochondrial DNA (mtDNA) is DNA that is located in mitochondria. ...

See also

• Polymerase chain reaction
• RNA polymerase

PCR tubes in a stand after a colony PCR The polymerase chain reaction (PCR) is a biochemistry and molecular biology technique[1] for exponentially amplifying DNA, via enzymatic replication, without using a living organism (such as E. coli or yeast). ... RNAP from pictured during elongation. ...

References

Citations

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 links

• Eukaryotic DNA Polymerases: Proposal for a Revised Nomenclature
• DNA Polymerases: Custom Search Engine
• Annual Review of Biochemistry: EUKARYOTIC DNA POLYMERASES
• DNA polymerase: PDB molecule of the month
• Unusual repair mechanism in DNA polymerase lambda, Ohio State University, July 25, 2006.
• MeSH DNA+polymerases