title: The catalytic function of the Rev1 dCMP transferase is required in a lesion-specific manner for translesion synthesis and base damage-induced mutagenesis.
abstract: The Rev1-Polzeta pathway is believed to be the major mechanism of translesion DNA synthesis and base damage-induced mutagenesis in eukaryotes. While it is widely believed that Rev1 plays a non-catalytic function in translesion synthesis, the role of its dCMP transferase activity remains uncertain. To determine the relevance of its catalytic function in translesion synthesis, we separated the Rev1 dCMP transferase activity from its non-catalytic function in yeast. This was achieved by mutating two conserved amino acid residues in the catalytic domain of Rev1, i.e. D467A/E468A, where its catalytic function was abolished but its non-catalytic function remained intact. In this mutant strain, whereas translesion synthesis and mutagenesis of UV radiation were fully functional, those of a site-specific 1,N(6)-ethenoadenine were severely deficient. Specifically, the predominant A-->G mutations resulting from C insertion opposite the lesion were abolished. Therefore, translesion synthesis and mutagenesis of 1,N(6)-ethenoadenine require the catalytic function of the Rev1 dCMP transferase, in contrast to those of UV lesions, which only require the non-catalytic function of Rev1. These results show that the catalytic function of the Rev1 dCMP transferase is required in a lesion-specific manner for translesion synthesis and base damage-induced mutagenesis.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jillian
authors.initials: J
authors.lastname: Wang
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D055162:Biocatalysis; D004247:DNA / Q000096:biosynthesis; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D016296:Mutagenesis; D009154:Mutation; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
chemical_list: D000225:Adenine; D004247:DNA; D018736:DNA Adducts; D004259:DNA-Directed DNA Polymerase; D009713:Nucleotidyltransferases; D029701:Saccharomyces cerevisiae Proteins; C004981:1,N(6)-ethenoadenine; C425929:DNA polymerase zeta; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases
references.citation: DNA Repair (Amst). 2005 Sep 28;4(10):1182-8
references.pmid: 15950550
references.citation: Nucleic Acids Res. 2004 Nov 02;32(19):5820-6
references.pmid: 15523096
references.citation: Mol Cell. 2006 Jul 21;23(2):265-71
references.pmid: 16857592
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6876-80
references.pmid: 9618506
references.citation: Nature. 2002 Dec 19-26;420(6917):860-7
references.pmid: 12490959
references.citation: Langenbecks Arch Surg. 2006 Sep;391(5):499-510
references.pmid: 16909291
references.citation: Mol Gen Genet. 1985;200(1):80-5
references.pmid: 3897794
references.citation: Genes Dev. 1998 Oct 1;12(19):3137-43
references.pmid: 9765213
references.citation: Cancer Surv. 1996;28:21-31
references.pmid: 8977026
references.citation: J Bacteriol. 1989 Oct;171(10):5659-67
references.pmid: 2676986
references.citation: Biochemistry. 2003 Sep 30;42(38):11253-62
references.pmid: 14503875
references.citation: Science. 1999 Feb 12;283(5404):1001-4
references.pmid: 9974380
references.citation: Nucleic Acids Res. 2004 Feb 11;32(3):1122-30
references.pmid: 14960722
references.citation: Nucleic Acids Res. 2000 Dec 1;28(23):4717-24
references.pmid: 11095682
references.citation: Nucleic Acids Res. 2006 Jan 13;34(2):417-25
references.pmid: 16415180
references.citation: EMBO J. 2003 Dec 15;22(24):6621-30
references.pmid: 14657033
references.citation: J Biol Chem. 2001 Jun 1;276(22):18717-21
references.pmid: 11376002
references.citation: J Bacteriol. 1989 Jan;171(1):230-7
references.pmid: 2492497
references.citation: Mutat Res. 1999 Mar 8;424(1-2):59-69
references.pmid: 10064850
references.citation: Mol Microbiol. 2000 Aug;37(3):549-54
references.pmid: 10931348
references.citation: Nucleic Acids Res. 2000 Nov 1;28(21):4138-46
references.pmid: 11058110
references.citation: DNA Repair (Amst). 2005 Dec 8;4(12):1399-409
references.pmid: 16181813
references.citation: Nucleic Acids Res. 1999 Nov 15;27(22):4468-75
references.pmid: 10536157
references.citation: Mutat Res. 2000 Oct 16;461(2):133-43
references.pmid: 11018586
references.citation: Nature. 2003 Sep 11;425(6954):188-91
references.pmid: 12968183
references.citation: Cancer Res. 2000 Aug 1;60(15):4098-104
references.pmid: 10945616
references.citation: Mol Cell Biol. 2000 Oct;20(19):7099-108
references.pmid: 10982826
references.citation: Biochemistry. 1996 Sep 3;35(35):11487-92
references.pmid: 8784204
references.citation: Nucleic Acids Res. 2008 Mar;36(4):1300-8
references.pmid: 18184697
references.citation: Nucleic Acids Res. 2004 Jul 29;32(13):3984-94
references.pmid: 15284331
references.citation: Methods Enzymol. 1995;262:232-56
references.pmid: 8594351
references.citation: Genetics. 2005 Feb;169(2):575-82
references.pmid: 15520252
references.citation: J Biol Chem. 2002 Jan 25;277(4):3040-6
references.pmid: 11711549
references.citation: Drug Metab Rev. 1994;26(1-2):349-71
references.pmid: 8082574
references.citation: EMBO J. 1999 Jun 15;18(12):3491-501
references.pmid: 10369688
references.citation: Methods Enzymol. 1991;194:182-7
references.pmid: 2005786
references.citation: J Biol Chem. 2001 Nov 23;276(47):43487-90
references.pmid: 11579108
references.citation: J Exp Med. 2006 Feb 20;203(2):319-23
references.pmid: 16476771
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4186-91
references.pmid: 10760286
references.citation: Mol Cancer Res. 2009 Feb;7(2):247-54
references.pmid: 19176310
references.citation: Science. 1996 Jun 14;272(5268):1646-9
references.pmid: 8658138
references.citation: Nucleic Acids Res. 2002 Apr 1;30(7):1630-8
references.pmid: 11917024
references.citation: Nature. 1996 Aug 22;382(6593):729-31
references.pmid: 8751446
references.citation: Science. 2005 Sep 30;309(5744):2219-22
references.pmid: 16195463