title: Oxidative damage and mutagenesis in Saccharomyces cerevisiae: genetic studies of pathways affecting replication fidelity of 8-oxoguanine.
abstract: Oxidative damage to DNA constitutes a major threat to the faithful replication of DNA in all organisms and it is therefore important to understand the various mechanisms that are responsible for repair of such damage and the consequences of unrepaired damage. In these experiments, we make use of a reporter system in Saccharomyces cerevisiae that can measure the specific increase of each type of base pair mutation by measuring reversion to a Trp+ phenotype. We demonstrate that increased oxidative damage due to the absence of the superoxide dismutase gene, SOD1, increases all types of base pair mutations and that mismatch repair (MMR) reduces some, but not all, types of mutations. By analyzing various strains that can revert only via a specific CG→AT transversion in backgrounds deficient in Ogg1 (encoding an 8-oxoG glycosylase), we can study mutagenesis due to a known 8-oxoG base. We show as expected that MMR helps prevent mutagenesis due to this damaged base and that Pol η is important for its accurate replication. In addition we find that its accurate replication is facilitated by template switching, as loss of either RAD5 or MMS2 leads to a significant decrease in accurate replication. We observe that these ogg1 strains accumulate revertants during prolonged incubation on plates, in a process most likely due to retromutagenesis.
authors.affiliation: Department of Biology, Emory University, Atlanta, Georgia 30322.
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Shockley
authors.forename: David W
authors.initials: DW
authors.lastname: Doo
authors.forename: Gina P
authors.initials: GP
authors.lastname: Rodriguez
authors.forename: Gray F
authors.initials: GF
authors.lastname: Crouse
mesh_terms: D004249:DNA Damage / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D016296:Mutagenesis / Q000235:genetics; D009154:Mutation; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: C112520:MMS2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C024829:8-hydroxyguanine; D006147:Guanine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D044767:Ubiquitin-Protein Ligases; D045647:DNA Glycosylases; C505160:Ogg1 protein, S cerevisiae; C076225:RAD5 protein, S cerevisiae; D004265:DNA Helicases
keywords: mismatch repair; oxidative damage; retromutagenesis; template switching; translesion synthesis
references.citation: Nat Genet. 2000 Aug;25(4):458-61
references.pmid: 10932195
references.citation: J Biol Chem. 1996 May 24;271(21):12275-80
references.pmid: 8647826
references.citation: Mol Cell Biol. 2005 Mar;25(6):2169-76
references.pmid: 15743815
references.citation: Nature. 2008 Dec 18;456(7224):915-20
references.pmid: 19092928
references.citation: Mutat Res. 2005 Dec 11;591(1-2):45-59
references.pmid: 16054172
references.citation: Am J Transl Res. 2010 May 15;2(3):254-84
references.pmid: 20589166
references.citation: Trends Biochem Sci. 2012 Apr;37(4):162-72
references.pmid: 22285516
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6153-8
references.pmid: 22474380
references.citation: PLoS Genet. 2013;9(8):e1003682
references.pmid: 23935538
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15954-9
references.pmid: 16247017
references.citation: J Biol Chem. 2002 Mar 29;277(13):11135-42
references.pmid: 11801590
references.citation: Cancer Lett. 2012 Dec 31;327(1-2):26-47
references.pmid: 22293091
references.citation: Mol Cell. 2005 Mar 4;17(5):709-20
references.pmid: 15749020
references.citation: Math Biosci. 2002 Apr;176(2):237-52
references.pmid: 11916511
references.citation: Annu Rev Microbiol. 2003;57:395-418
references.pmid: 14527285
references.citation: Chem Biodivers. 2011 Sep;8(9):1571-615
references.pmid: 21922653
references.citation: J Biol Chem. 2003 Feb 28;278(9):6824-30
references.pmid: 12475988
references.citation: Nat Chem Biol. 2009 Feb;5(2):82-90
references.pmid: 19148176
references.citation: DNA Repair (Amst). 2010 Jun 4;9(6):604-16
references.pmid: 20399712
references.citation: DNA Repair (Amst). 2007 Apr 1;6(4):481-8
references.pmid: 17127104
references.citation: Free Radic Biol Med. 2002 Jul 1;33(1):1-14
references.pmid: 12086677
references.citation: Proc Natl Acad Sci U S A. 1996 May 28;93(11):5197-202
references.pmid: 8643552
references.citation: Nucleic Acids Res. 2004 Sep 23;32(17):5003-10
references.pmid: 15388802
references.citation: Curr Biol. 2002 Jun 4;12(11):912-8
references.pmid: 12062055
references.citation: Nucleic Acids Res. 2007;35(22):7545-56
references.pmid: 18055498
references.citation: Mol Cell. 2011 Aug 19;43(4):649-62
references.pmid: 21855803
references.citation: Exp Gerontol. 2010 Aug;45(7-8):478-88
references.pmid: 20096766
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18877-82
references.pmid: 19020090
references.citation: Methods Enzymol. 2006;409:195-213
references.pmid: 16793403
references.citation: Chem Res Toxicol. 2006 Apr;19(4):491-505
references.pmid: 16608160
references.citation: J Biol Chem. 1993 Mar 15;268(8):5849-55
references.pmid: 8449951
references.citation: Structure. 2010 Nov 10;18(11):1463-70
references.pmid: 21070945
references.citation: Mutat Res. 2008 Jul-Aug;659(1-2):4-14
references.pmid: 18083609
references.citation: Mutat Res. 2003 Oct 29;531(1-2):231-51
references.pmid: 14637258
references.citation: Mol Cell. 1999 Sep;4(3):439-44
references.pmid: 10518225
references.citation: Bioessays. 2011 Apr;33(4):255-9
references.pmid: 21290398
references.citation: Curr Biol. 1996 Aug 1;6(8):968-80
references.pmid: 8805338
references.citation: Genetics. 2005 Jul;170(3):1423-6
references.pmid: 15911571
references.citation: Nat Rev Genet. 2001 Jul;2(7):504-15
references.pmid: 11433357
references.citation: Cancer Sci. 2007 Apr;98(4):465-70
references.pmid: 17425590
references.citation: Neuroscience. 2007 Apr 14;145(4):1233-48
references.pmid: 17303344
references.citation: Mutat Res. 2011 Nov-Dec;728(3):107-17
references.pmid: 21763452
references.citation: Methods Enzymol. 2002;350:3-41
references.pmid: 12073320
references.citation: J Bacteriol. 1991 Sep;173(18):5918-20
references.pmid: 1885557
references.citation: DNA Repair (Amst). 2002 Dec 5;1(12):995-1001
references.pmid: 12531009
references.citation: Biol Chem. 2006 Apr;387(4):373-9
references.pmid: 16606334
references.citation: Chem Res Toxicol. 1998 Jun;11(6):666-73
references.pmid: 9625735
references.citation: J Bacteriol. 2003 Mar;185(5):1701-4
references.pmid: 12591888
references.citation: J Biol Chem. 1999 Sep 17;274(38):26668-82
references.pmid: 10480869
references.citation: DNA Repair (Amst). 2005 Feb 3;4(2):141-8
references.pmid: 15590322
references.citation: Carcinogenesis. 2009 Jan;30(1):2-10
references.pmid: 18978338
references.citation: Mol Cell. 2003 Oct;12(4):959-70
references.pmid: 14580346
references.citation: Nat Rev Cancer. 2011 Mar;11(3):218-27
references.pmid: 21346784
references.citation: Mutat Res. 2007 Jan 3;614(1-2):24-36
references.pmid: 16879837
references.citation: Mutat Res. 2010 Nov 28;703(1):32-6
references.pmid: 20542139
references.citation: Mol Cell Biol. 2009 Oct;29(19):5316-26
references.pmid: 19635811
references.citation: J Bacteriol. 2004 Aug;186(15):4846-52
references.pmid: 15262917
references.citation: Yeast. 2008 Dec;25(12):903-12
references.pmid: 19160453
references.citation: Mutat Res. 2004 Sep;567(1):1-61
references.pmid: 15341901
references.citation: Curr Opin Struct Biol. 2011 Jun;21(3):358-69
references.pmid: 21482102
references.citation: Mol Cell. 2010 Jun 11;38(5):649-61
references.pmid: 20541998
references.citation: Cancer Res. 2006 Mar 1;66(5):2497-9
references.pmid: 16510562
references.citation: Mutat Res. 2010 Nov 28;703(1):18-23
references.pmid: 20696268
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15487-91
references.pmid: 9860995
references.citation: Science. 1999 Aug 6;285(5429):901-6
references.pmid: 10436161
references.citation: Math Biosci. 2005 Aug;196(2):198-214
references.pmid: 15950991
references.citation: Methods Mol Biol. 2009;554:165-81
references.pmid: 19513674
references.citation: Mutat Res. 2003 Oct 29;531(1-2):37-80
references.pmid: 14637246
references.citation: Mutat Res. 2001 Sep 1;480-481:85-95
references.pmid: 11506802
references.citation: Free Radic Biol Med. 2002 Jun 15;32(12):1244-53
references.pmid: 12057762
references.citation: Mutat Res. 2010 Nov 28;703(1):59-65
references.pmid: 20601098
references.citation: J Biol Chem. 2000 Mar 17;275(11):8233-9
references.pmid: 10713149
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5785-90
references.pmid: 22451939
references.citation: Mutat Res. 2002 Dec 29;510(1-2):131-40
references.pmid: 12459449
references.citation: Mutat Res. 2011 Jun 3;711(1-2):193-201
references.pmid: 21216256
references.citation: Chem Rev. 2006 Feb;106(2):474-88
references.pmid: 16464015
references.citation: Math Biosci. 2007 Oct;209(2):500-13
references.pmid: 17462675
references.citation: J Biol Chem. 2002 Mar 8;277(10):8260-6
references.pmid: 11756455
references.citation: Mol Cell Biol. 2004 Jan;24(1):465-74
references.pmid: 14673178
references.citation: Methods. 2000 Jan;20(1):4-17
references.pmid: 10610800
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3578-82
references.pmid: 9520408
references.citation: Prog Neurobiol. 2011 Jul;94(2):166-200
references.pmid: 21550379
references.citation: J Biol Chem. 1998 Aug 14;273(33):21276-81
references.pmid: 9694887
references.citation: Cancer Lett. 2008 Jul 18;266(1):60-72
references.pmid: 18374480
references.citation: Curr Genet. 1999 Oct;36(4):195-200
references.pmid: 10541856
references.citation: Genetics. 1991 May;128(1):59-67
references.pmid: 1648005
references.citation: Cell Res. 2008 Jan;18(1):99-113
references.pmid: 18166982
references.citation: Nucleic Acids Res. 2007;35(22):7497-504
references.pmid: 17947327
references.citation: Mutagenesis. 2006 Nov;21(6):361-7
references.pmid: 17065161
references.citation: Annu Rev Biochem. 2008;77:755-76
references.pmid: 18173371