Eukaryotic DNA Polymerases: Proposal for a Revised Nomenclature
2001; Elsevier BV; Volume: 276; Issue: 47 Linguagem: Inglês
10.1074/jbc.r100056200
ISSN1083-351X
AutoresPeter Burgers, Eugene V. Koonin, Elspeth A. Bruford, Luis Blanco, Kenneth C. Burtis, Michael F. Christman, William C. Copeland, Errol C. Friedberg, Fumio Hanaoka, David C. Hinkle, Christopher W. Lawrence, Makoto Nakanishi, Haruo Ohmori, Louise Prakash, Satya Prakash, Claude‐Agnès Reynaud, Akio Sugino, Takeshi Todo, Zhigang Wang, Jean-Claude Weill, Roger Woodgate,
Tópico(s)RNA and protein synthesis mechanisms
Resumopolymerase In 1975, a Greek letter nomenclature system was introduced to designate DNA polymerases from mammalian cells (1Weissbach A. Baltimore D. Bollum F. Gallo R. Korn D. Science. 1975; 190: 401-402Crossref PubMed Scopus (126) Google Scholar). Ten years ago, progress in the biochemical analysis of eukaryotic DNA polymerases and in the isolation of their genes, particularly in the yeast Saccharomyces cerevisiae, necessitated a revision of the Greek letter nomenclature system and an expansion to include all eukaryotic organisms (2Burgers P.M.J. Bambara R.A. Campbell J.L. Chang L.M.S. Downey K.M. Hubscher U. Lee M.Y.W.T. Linn S.M. So A.G. Spadari S. Eur. J. Biochem. 1990; 191: 617-618Crossref PubMed Scopus (103) Google Scholar). Until a few years ago, this system sufficed to designate the six known DNA polymerases α, β, γ, δ, ε, and ζ. Three lines of research have greatly expanded the number of DNA polymerases in the last two years. First, with the advent of the human and mouse genome projects, sequence analysis allowed the identification of additional putative DNA polymerases related to Escherichia coli Pol I1 and mammalian Pol β (3Sharief F.S. Vojta P.J. Ropp P.A. Copeland W.C. Genomics. 1999; 59: 90-96Crossref PubMed Scopus (99) Google Scholar, 4Aoufouchi S. Flatter E. Dahan A. Faili A. Bertocci B. Storck S. Delbos F. Cocea L. Gupta N. Weill J.C. Reynaud C.A. Nucleic Acids Res. 2000; 28: 3684-3693Crossref PubMed Google Scholar, 5Dominguez O. Ruiz J.F. Lain de Lera T. Garcia-Diaz M. Gonzalez M.A. Kirchhoff T. Martinez A.C. Bernad A. Blanco L. EMBO J. 2000; 19: 1731-1742Crossref PubMed Google Scholar, 6Garcia-Diaz M. Dominguez O. Lopez-Fernandez L.A. de Lera L.T. Saniger M.L. Ruiz J.F. Parraga M. Garcia-Ortiz M.J. Kirchhoff T. del Mazo J. Bernad A. Blanco L. J. Mol. Biol. 2000; 301: 851-867Crossref PubMed Scopus (251) Google Scholar). Second, the realization that E. coli UmuC and DinB, yeast RAD30, and the human xeroderma pigmentosum variant genes encode DNA polymerases has led to the identification of several additional DNA polymerases in this superfamily (7Tang M. Shen X. Frank E.G. O'Donnell M. Woodgate R. Goodman M.F. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 8919-8924Crossref PubMed Scopus (489) Google Scholar, 8Reuven N.B. Arad G. Maor-Shoshani A. Livneh Z. J. Biol. Chem. 1999; 274: 31763-31766Abstract Full Text Full Text PDF PubMed Scopus (316) Google Scholar, 9Wagner J. Gruz P. Kim S.R. Yamada M. Matsui K. Fuchs R.P. Nohmi T. Mol. Cell. 1999; 4: 281-286Abstract Full Text Full Text PDF PubMed Scopus (409) Google Scholar, 10Johnson R.E. Prakash S. Prakash L. Science. 1999; 283: 1001-1004Crossref PubMed Scopus (701) Google Scholar, 11Masutani C. Kusumoto R. Yamada A. Dohmae N. Yokoi M. Yuasa M. Araki M. Iwai S. Takio K. Hanaoka F. Nature. 1999; 399: 700-704Crossref PubMed Scopus (1166) Google Scholar). Third, advanced search algorithms based on DNA polymerase structure-function relationships have allowed the prediction of additional putative DNA polymerases, which prediction was later confirmed by biochemical analysis (12Aravind L. Koonin E.V. Nucleic Acids Res. 1998; 26: 3746-3752Crossref PubMed Scopus (210) Google Scholar, 13Aravind L. Koonin E.V. Nucleic Acids Res. 1999; 27: 1609-1618Crossref PubMed Scopus (277) Google Scholar, 14Wang Z. Castaño I.B. De Las Peñas A. Adams C. Christman M.F. Science. 2000; 289: 774-779Crossref PubMed Scopus (163) Google Scholar). This rapid proliferation of DNA polymerases, either predicted from search algorithms or experimentally verified, resulted in an inevitable confusion and contradiction in the naming of these enzymes. Therefore, the scientists active in this field are proposing a revised nomenclature to resolve contradictions in polymerase designations and to ensure that the naming of subsequent enzymes be under the advice of an established nomenclature committee. A novel human DNA polymerase in the X family of DNA polymerases had independently been identified by several groups, but the enzyme was named Pol β2 by one group (15Nagasawa K. Kitamura K. Yasui A. Nimura Y. Ikeda K. Hirai M. Matsukage A. Nakanishi M. J. Biol. Chem. 2000; 275: 31233-31238Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar) and Pol λ by two other groups (4Aoufouchi S. Flatter E. Dahan A. Faili A. Bertocci B. Storck S. Delbos F. Cocea L. Gupta N. Weill J.C. Reynaud C.A. Nucleic Acids Res. 2000; 28: 3684-3693Crossref PubMed Google Scholar,6Garcia-Diaz M. Dominguez O. Lopez-Fernandez L.A. de Lera L.T. Saniger M.L. Ruiz J.F. Parraga M. Garcia-Ortiz M.J. Kirchhoff T. del Mazo J. Bernad A. Blanco L. J. Mol. Biol. 2000; 301: 851-867Crossref PubMed Scopus (251) Google Scholar). In conformity with the new proposed rules for naming DNA polymerases, the name Pol λ will be adopted for this enzyme. A putative DNA polymerase with homology to E. coli DNA polymerase I, which had been designated Pol θ for the human enzyme (3Sharief F.S. Vojta P.J. Ropp P.A. Copeland W.C. Genomics. 1999; 59: 90-96Crossref PubMed Scopus (99) Google Scholar) but Pol η for the Drosophila enzyme (16Burtis K.C. Harris P.V. Curr. Biol. 1997; 7: R743-R744Abstract Full Text Full Text PDF PubMed Google Scholar, 17Harris P.V. Molecular cloning and expression of Drosophila mus308 and human POLQ, a new class of eukaryotic DNA polymerase with potential involvement in the repair of DNA interstrand crosslinks.Ph.D. thesis. University of California, Davis1999Google Scholar), will be called Pol θ as Pol η is already used to designate the unrelated yeast RAD30 encoded DNA polymerase (10Johnson R.E. Prakash S. Prakash L. Science. 1999; 283: 1001-1004Crossref PubMed Scopus (701) Google Scholar). A human homologue of E. coli DinB, i.e. the human DINB1gene, had independently been identified by several groups. However, the enzyme was designated DNA Pol θ by one group (18Johnson R.E. Prakash S. Prakash L. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 3838-3843Crossref PubMed Scopus (165) Google Scholar) and Pol κ by other groups (19Ohashi E. Ogi T. Kusumoto R. Iwai S. Masutani C. Hanaoka F. Ohmori H. Genes Dev. 2000; 14: 1589-1594PubMed Google Scholar, 20Ohashi E. Bebenek K. Matsuda T. Feaver W.J. Gerlach V.L. Friedberg E.C. Ohmori H. Kunkel T.A. J. Biol. Chem. 2000; 275: 39678-39684Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar, 21Zhang Y. Yuan F. Wu X. Wang M. Rechkoblit O. Taylor J.S. Geacintov N.E. Wang Z. Nucleic Acids Res. 2000; 28: 4138-4146Crossref PubMed Google Scholar). We have chosen to adopt the name Pol κ for the mammalian DINB1 enzyme. Finally, the name Pol κ had also been assigned to a DNA polymerase encoded by the S. cerevisiae TRF4 gene, required for sister chromatid cohesion (14Wang Z. Castaño I.B. De Las Peñas A. Adams C. Christman M.F. Science. 2000; 289: 774-779Crossref PubMed Scopus (163) Google Scholar). To maintain a coherent and logical nomenclature across eukaryotic phyla, the DNA polymerase encoded by TRF4 has been renamed Pol ς. Table I gives an overview of the currently known eukaryotic DNA polymerases.Table IProposed nomenclature for eukaryotic DNA polymerasesGreek nameHUGO nameClassOther namesProposed main functionα (alpha)POLABPOL1DNA replicationβ (beta)POLBXBase excision repairγ (gamma)POLGAMIP1Mitochondrial replicationδ (delta)POLD1BPOL3DNA replicationε (epsilon)POLEBPOL2DNA replicationζ (zeta)POLZBREV3Bypass synthesisη (eta)POLHYRAD30, XPVBypass synthesisθ (theta)POLQAmus308, etaDNA repairι (iota)POLIYRAD30BBypass synthesisκ (kappa)POLKYDinB1, thetaBypass synthesisλ (lambda)POLLXPOL4, beta2Base excision repairμ (mu)POLMXNon-homologous end joiningς (sigma)POLSXTRF4, kappaSister chromatid cohesionREV1LYREV1Bypass synthesisTDTXAntigen receptor diversityS. cerevisiae genes (in italics) and conflicting names are listed under “Other Names.” See text for details. Open table in a new tab S. cerevisiae genes (in italics) and conflicting names are listed under “Other Names.” See text for details. To avoid future confusion and contradictions in DNA polymerase designations, we are proposing the following rules. 1) The human genome nomenclature committee (www.gene.ucl.ac.uk/nomenclature; E-mail: [email protected]) has agreed to coordinate the nomenclature of all eukaryotic DNA polymerases. A polymerase should only be given a Greek letter designation with approval by the HUGO nomenclature committee. Greek letter denominations for putative DNA polymerases can be reserved pending experimental verification. As usual, the burden of proof remains acceptance of the experimental work in a peer-reviewed scientific journal. 2) In general, all DNA polymerases will follow the one gene→one polymerase rule. However, the TRF family of DNA polymerases, required for sister chromatid cohesion, will constitute an exception to this rule. Studies in S. cerevisiae, Schizosaccharomyces pombe, and mammalian cells have shown these to be multigene families with two members (TRF4 and TRF5) in S. cerevisiae (14Wang Z. Castaño I.B. De Las Peñas A. Adams C. Christman M.F. Science. 2000; 289: 774-779Crossref PubMed Scopus (163) Google Scholar), as many as six possible family members (the cidgenes) in S. pombe (22Wang S.W. Toda T. MacCallum R. Harris A.L. Norbury C. Mol. Cell. Biol. 2000; 20: 3234-3244Crossref PubMed Scopus (58) Google Scholar), and at least two identified family members in human cells. Because of the potential for a multitude of DNA polymerases involved in sister chromatid cohesion and related processes, the TRF4-related DNA polymerases will all be designated Pol ς, with each individual family member designated with a suffix, i.e. Pol ς1. 3) A class of nucleotidyltransferases with S. cerevisiae REV1 as founding member uniquely inserts deoxycytidylate residues, preferentially opposite abasic template sites (23Nelson J.R. Lawrence C.W. Hinkle D.C. Nature. 1996; 382: 729-731Crossref PubMed Scopus (511) Google Scholar). Because of its unique enzymatic character, no polymerase designation has been given to this enzyme even though sequence-based considerations place it in the Y class of DNA polymerases (24Ohmori H. Friedberg E. Fuchs R. Goodman M. Hanaoka F. Hinkle D. Kunkel T. Lawrence C. Livneh Z. Nohmi T. Prakash L. Prakash S. Todo T. Walker G. Wang Z. Woodgate R. Mol. Cell. 2001; 8: 7-8Abstract Full Text Full Text PDF PubMed Scopus (754) Google Scholar). Similar considerations apply to terminal deoxynucleotidyltransferase, an X class template-independent enzyme (Table I). DNA polymerases can be classified in six main groups based upon phylogenetic relationships with E. coli Pol I (class A),E. coli Pol II (class B), E. coli Pol III (class C), Euryarchaeotic Pol II (class D), human Pol β (class X), and E. coli UmuC/DinB and eukaryotic RAD30/xeroderma pigmentosum variant (class Y) (24Ohmori H. Friedberg E. Fuchs R. Goodman M. Hanaoka F. Hinkle D. Kunkel T. Lawrence C. Livneh Z. Nohmi T. Prakash L. Prakash S. Todo T. Walker G. Wang Z. Woodgate R. Mol. Cell. 2001; 8: 7-8Abstract Full Text Full Text PDF PubMed Scopus (754) Google Scholar, 25Ito J. Braithwaite D.K. Nucleic Acids Res. 1991; 19: 4045-4057Crossref PubMed Scopus (305) Google Scholar, 26Braithwaite D.K. Ito J. Nucleic Acids Res. 1993; 21: 787-802Crossref PubMed Scopus (545) Google Scholar, 27Cann I.K. Ishino Y. Genetics. 1999; 152: 1249-1267Crossref PubMed Google Scholar). All known eukaryotic enzymes are either class A, class B, class X, or class Y enzymes (Table I). No eukaryotic homologs of class C or class D DNA polymerases were detected (www.ncbi.nlm.nih.gov/) despite detailed sequence searches using the PSI-BLAST program (28Altschul S.F. Madden T.L. Schaffer A.A. Zhang J. Zhang Z. Miller W. Lipman D.J. Nucleic Acids Res. 1997; 25: 3389-3402Crossref PubMed Scopus (61168) Google Scholar, 29Leipe D.D. Aravind L. Koonin E.V. Nucleic Acids Res. 1999; 27: 3389-3401Crossref PubMed Scopus (274) Google Scholar). For each distinct human DNA polymerase we searched for putative orthologs in the completely sequenced genomes of S. cerevisiae, S. pombe, Drosophila melanogaster, Caenorhabditis elegans, and Arabidopsis thaliana (TableII). Clear and unambiguous orthologs exist in all eukaryotes for the class B enzymes Pol α, Pol δ, and Pol ε, required for nuclear DNA replication, and also for Pol ζ, a class B enzyme involved in mutagenic DNA replication. These enzymes have been extensively reviewed and will not further be discussed here (30Sugino A. Trends Biochem. Sci. 1995; 20: 319-323Abstract Full Text PDF PubMed Scopus (102) Google Scholar, 31Lawrence C.W. Hinkle D.C. Cancer Surv. 1996; 28: 21-31PubMed Google Scholar, 32Hindges R. Hubscher U. Biol. Chem. 1997; 378: 345-362Crossref PubMed Google Scholar, 33Burgers P.M. Chromosoma. 1998; 107: 218-227Crossref PubMed Scopus (169) Google Scholar, 34Lawrence C.W. Maher V.M. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2001; 356: 41-46Crossref PubMed Google Scholar).Table IIOrthologs of human DNA polymerases in five completely sequenced eukaryotic organismsPolymerases are grouped by class and by proposed function. Probable orthologous relationships were established by detecting bi-directional, genome-specific best hits in BLAST searches (62Tatusov R.L. Koonin E.V. Lipman D.J. Science. 1997; 278: 631-637Crossref PubMed Scopus (2826) Google Scholar). For each organism, we list the probable ortholog by gene name or GenBank accession number, followed by the lengthf the protein. For the Y class polymerases, the orthologous relationships were determined by phylogenetic analysis (24Ohmori H. Friedberg E. Fuchs R. Goodman M. Hanaoka F. Hinkle D. Kunkel T. Lawrence C. Livneh Z. Nohmi T. Prakash L. Prakash S. Todo T. Walker G. Wang Z. Woodgate R. Mol. Cell. 2001; 8: 7-8Abstract Full Text Full Text PDF PubMed Scopus (754) Google Scholar,63Gerlach V.L. Feaver W.J. Fischhaber P.L. Richardson J.A. Aravind L. Koonin E.V. Bebenek K. Kunkel T.A. Friedberg E.C. Cold Spring Harbor Symp. Quant. Biol. 2000; 65: 41-49Crossref PubMed Scopus (13) Google Scholar).2-a There are two Pol ς genes in human cells; the analysis was carried out with the TRF4–1 (POLS) gene, which encodes a protein with demonstrated DNA polymerase activity (M. F. Christman, unpublished results).2-b Pol η and Pol ι appear to have evolved through a lineage-specific duplication in animals, so these two paralogs together should be considered orthologous to the single counterpart in other organisms.2-c Alternative splice sites to produce larger forms of Pol κ from S. pombe and C. elegans have been proposed (45Johnson R.E. Washington M.T. Prakash S. Prakash L. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 12224-12226Crossref PubMed Scopus (131) Google Scholar). Open table in a new tab Polymerases are grouped by class and by proposed function. Probable orthologous relationships were established by detecting bi-directional, genome-specific best hits in BLAST searches (62Tatusov R.L. Koonin E.V. Lipman D.J. Science. 1997; 278: 631-637Crossref PubMed Scopus (2826) Google Scholar). For each organism, we list the probable ortholog by gene name or GenBank accession number, followed by the lengthf the protein. For the Y class polymerases, the orthologous relationships were determined by phylogenetic analysis (24Ohmori H. Friedberg E. Fuchs R. Goodman M. Hanaoka F. Hinkle D. Kunkel T. Lawrence C. Livneh Z. Nohmi T. Prakash L. Prakash S. Todo T. Walker G. Wang Z. Woodgate R. Mol. Cell. 2001; 8: 7-8Abstract Full Text Full Text PDF PubMed Scopus (754) Google Scholar,63Gerlach V.L. Feaver W.J. Fischhaber P.L. Richardson J.A. Aravind L. Koonin E.V. Bebenek K. Kunkel T.A. Friedberg E.C. Cold Spring Harbor Symp. Quant. Biol. 2000; 65: 41-49Crossref PubMed Scopus (13) Google Scholar). 2-a There are two Pol ς genes in human cells; the analysis was carried out with the TRF4–1 (POLS) gene, which encodes a protein with demonstrated DNA polymerase activity (M. F. Christman, unpublished results). 2-b Pol η and Pol ι appear to have evolved through a lineage-specific duplication in animals, so these two paralogs together should be considered orthologous to the single counterpart in other organisms. 2-c Alternative splice sites to produce larger forms of Pol κ from S. pombe and C. elegans have been proposed (45Johnson R.E. Washington M.T. Prakash S. Prakash L. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 12224-12226Crossref PubMed Scopus (131) Google Scholar). Two enzymes of this set of related DNA polymerases may be involved in short-patch DNA excision repair. Both human Pol β and human Pol λ show deoxyribose phosphate lyase activity, indicative of their ability to process intermediates in the DNA glycosylase-initiated repair of damaged bases (35Matsumoto Y. Kim K. Science. 1995; 269: 699-702Crossref PubMed Scopus (656) Google Scholar, 36Garcia-Diaz M. Bebenek K. Kunkel T.A. Blanco L. J. Biol. Chem. 2001; 276: 34659-34663Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar). A function for Pol μ in somatic hypermutation has been proposed based upon its low fidelity of DNA synthesis in vitro and its cell type-specific expression pattern in mammals (5Dominguez O. Ruiz J.F. Lain de Lera T. Garcia-Diaz M. Gonzalez M.A. Kirchhoff T. Martinez A.C. Bernad A. Blanco L. EMBO J. 2000; 19: 1731-1742Crossref PubMed Google Scholar, 37Reynaud C.A. Frey S. Aoufouchi S. Faili A. Bertocci B. Dahan A. Flatter E. Delbos F. Storck S. Zober C. Weill J.C. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2001; 356: 91-97Crossref PubMed Google Scholar). Moreover, a more general role of Pol μ in non-homologous end joining of double-stranded DNA breaks has also been proposed (38Ruiz J.F. Dominguez O. Lain de Lera T. Garcia-Diaz M. Bernad A. Blanco L. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2001; 356: 99-109Crossref PubMed Google Scholar). Interestingly, neither of these three enzymes is found in D. melanogasteror in C. elegans, suggesting that base damage in these organisms is exclusively repaired by the long-patch mechanism, requiring the nuclease FEN1 and the replication clamp proliferating cell nuclear antigen (39Klungland A. Lindahl T. EMBO J. 1997; 16: 3341-3348Crossref PubMed Scopus (678) Google Scholar, 40Kim K. Biade S. Matsumoto Y. J. Biol. Chem. 1998; 273: 8842-8848Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar). The virtual lack of sensitivity to several DNA-damaging agents in a S. cerevisiae null mutant of the single β-like DNA polymerase gene POL4, which appears to be the ortholog of Pol λ, strongly suggests that base damage is efficiently repaired by the long-patch base excision repair pathway in this organism (41Prasad R. Widen S.G. Singhal R.K. Watkins J. Prakash L. Wilson S.H. Nucleic Acids Res. 1993; 21: 5301-5307Crossref PubMed Scopus (76) Google Scholar, 42Leem S.H. Ropp P.A. 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Pol η and Pol ι appeared to have evolved through a lineage-specific duplication in animals, so these two paralogs together should be considered orthologous to the single counterpart in other organisms. Orthologs are found in each of the five eukaryotic organisms investigated (Table II). Surprisingly, Pol ι was also found to possess deoxyribose-phosphate lyase activity, like Pol β and Pol λ, perhaps implicating it in a specialized form of base excision repair (56Tissier A. McDonald J.P. Frank E.G. Woodgate R. Genes Dev. 2000; 14: 1642-1650PubMed Google Scholar, 57Zhang Y. Yuan F. Wu X. Wang Z. Mol. Cell. Biol. 2000; 20: 7099-7108Crossref PubMed Scopus (190) Google Scholar, 58Bebenek K. Tissier A. Frank E.G. McDonald J.P. Prasad R. Wilson S.H. Woodgate R. Kunkel T.A. Science. 2001; 291: 2156-2159Crossref PubMed Scopus (172) Google Scholar). In contrast to the three bypass enzymes Pol η, Pol ι, and Pol κ, the related deoxycytidylate transferase Rev1, which is required for mutagenesis, is clearly represented in each organism (34Lawrence C.W. Maher V.M. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2001; 356: 41-46Crossref PubMed Google Scholar) (Table II). This DNA polymerase, which is very distantly related to the other members of the Pol X superfamily, is represented by two closely related paralogs in human, S. cerevisiae, D. melanogaster, and S. cerevisiae, four paralogs in S. pombe, and one highly conserved version in C. elegans and A. thaliana (Table II). In addition, humans have at least two, C. elegans at least nine, and A. thaliana at least one more distant members of this family of (predicted) polymerases (13Aravind L. Koonin E.V. Nucleic Acids Res. 1999; 27: 1609-1618Crossref PubMed Scopus (277) Google Scholar). 2E. V. Koonin, unpublished observations. Detailed phylogenetic analysis of this family remains to be performed. Pol ς is required for sister chromatid cohesion. DNA polymerase activity has only been demonstrated in the S. cerevisiae TRF4 gene product and the human TRF4–1 gene product (14Wang Z. Castaño I.B. De Las Peñas A. Adams C. Christman M.F. Science. 2000; 289: 774-779Crossref PubMed Scopus (163) Google Scholar). 3M. F. Christman, unpublished results. This DNA polymerase is unique in that the N-terminal domain contains the seven conserved motifs of the DNA and RNA helicase superfamily II, whereas the C-terminal shows strong sequence similarity to E. coli DNA polymerase I. Studies with a Drosophila Pol θ mutant, designated mus308, suggest a role for this enzyme in DNA repair of interstrand cross-links (59Harris P.V. Mazina O.M. Leonhardt E.A. Case R.B. Boyd J.B. Burtis K.C. Mol. Cell. Biol. 1996; 16: 5764-5771Crossref PubMed Scopus (103) Google Scholar,60Sekelsky J.J. Burtis K.C. Hawley R.S. Genetics. 1998; 148: 1587-1598Crossref PubMed Google Scholar). Fractionated extracts from Drosophila mus308 embryos lack a specific DNA polymerase activity present in extracts from wild type, suggesting that mus308 encodes a DNA polymerase (61Oshige M. Aoyagi N. Harris P.V. Burtis K.C. Sakaguchi K. Mutat. Res. 1999; 433: 183-192Crossref PubMed Scopus (32) Google Scholar). This bipartite DNA polymerase is not found in the two yeasts, but putative orthologs were detected in the other three eukaryotic species (TableII). Surprisingly, no ortholog for the mitochondrial DNA polymerase could be detected in A. thaliana. This could either indicate a gap in the data base for this organism or alternatively that mitochondrial DNA replication in plants is either performed by one of the other known DNA polymerases or by a novel DNA polymerase. Interestingly, the BLAST search for Pol θ in A. thaliana returned (in addition to the putative ortholog of Pol θ) two class A DNA polymerases with limited sequence similarity to Pol θ (E value of 10−15) but very strong sequence similarity to bacterial DNA polymerase I (E values of 10−43–10−48). Possibly, these two DNA polymerases could function in DNA replication of mitochondrial and/or chloroplast DNA. As mentioned above, two putative DNA polymerases exist in A. thaliana for which no orthologs have been found in human. One or both of these may well be required for replication of chloroplast DNA. Otherwise, additional enzyme(s) remain to be identified for replication of chloroplast DNA. Finally, the S. cerevisiae POL5 gene, as well as the homologous S. pombe Pol5 gene, shows only limited sequence similarity with class B DNA polymerases (30Sugino A. Trends Biochem. Sci. 1995; 20: 319-323Abstract Full Text PDF PubMed Scopus (102) Google Scholar). It contains a sequence that is conserved in the two yeasts and resembles the Mg2+ binding motif characteristic of the catalytic center of class B DNA polymerases. However, these proteins show significant sequence similarity to eukaryotic leucine zipper-containing transcription factors such as human MYBB1A. In accordance with the proposed new nomenclature rules this putative DNA polymerase has been provisionally designated Pol φ and the name POLF reserved with the HUGO nomenclature committee pending experimental verification.
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