title: A role for yeast and human translesion synthesis DNA polymerases in promoting replication through 3-methyl adenine.
abstract: 3-Methyl adenine (3meA), a minor-groove DNA lesion, presents a strong block to synthesis by replicative DNA polymerases (Pols). To elucidate the means by which replication through this DNA lesion is mediated in eukaryotic cells, here we carry out genetic studies in the yeast Saccharomyces cerevisiae treated with the alkylating agent methyl methanesulfonate. From the studies presented here, we infer that replication through the 3meA lesion in yeast cells can be mediated by the action of three Rad6-Rad18-dependent pathways that include translesion synthesis (TLS) by Pol(eta) or -zeta and an Mms2-Ubc13-Rad5-dependent pathway which presumably operates via template switching. We also express human Pols iota and kappa in yeast cells and show that they too can mediate replication through the 3meA lesion in yeast cells, indicating a high degree of evolutionary conservation of the mechanisms that control TLS in yeast and human cells. We discuss these results in the context of previous observations that have been made for the roles of Pols eta, iota, and kappa in promoting replication through the minor-groove N2-dG adducts.
authors: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX 77555-1061, USA.
authors: Robert E
authors: RE
authors: Johnson
authors: Sung-Lim
authors: SL
authors: Yu
authors: Satya
authors: S
authors: Prakash
authors: Louise
authors: L
authors: Prakash
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000378:metabolism; D001665:Binding Sites; D004265:DNA Helicases; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008741:Methyl Methanesulfonate / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007527:Isoenzymes; C112520:MMS2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C025946:3-methyladenine; D008741:Methyl Methanesulfonate; C471610:UBC13 protein, S cerevisiae; C471607:UBE2N protein, human; C114715:UBE2V2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D004259:DNA-Directed DNA Polymerase; D000251:Adenosine Triphosphatases; C076225:RAD5 protein, S cerevisiae; D004265:DNA Helicases; D008025:Ligases; D000225:Adenine
references: J Biol Chem. 2000 Mar 17;275(11):7447-50
references: 10713043
references: Nature. 2003 Sep 11;425(6954):188-91
references: 12968183
references: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3838-43
references: 10760255
references: Mol Cell Biol. 2000 May;20(10):3522-8
references: 10779341
references: EMBO J. 2000 Jul 3;19(13):3388-97
references: 10880451
references: Genes Dev. 2000 Jul 1;14(13):1642-50
references: 10887158
references: Nature. 2000 Aug 31;406(6799):1015-9
references: 10984059
references: Mol Cell Biol. 2001 Jan;21(1):185-8
references: 11113193
references: Carcinogenesis. 1980 Jul;1(7):595-606
references: 11219835
references: J Biol Chem. 2001 Mar 2;276(9):6861-6
references: 11106652
references: J Biol Chem. 2001 Mar 23;276(12):9077-82
references: 11054428
references: Genes Dev. 2001 Apr 15;15(8):945-54
references: 11316789
references: Mol Cell. 2001 Aug;8(2):417-26
references: 11545743
references: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14256-61
references: 11724965
references: Mol Cell Biol. 2002 Apr;22(7):2419-26
references: 11884624
references: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12093-8
references: 14527996
references: Mol Cell Biol. 2004 Jan;24(2):936-43
references: 14701763
references: Cell. 2004 Mar 19;116(6):803-16
references: 15035983
references: Mol Cell Biol. 2004 May;24(10):4267-74
references: 15121847
references: Biochemistry. 2004 May 18;43(19):5592-9
references: 15134433
references: Mol Gen Genet. 1985;200(1):86-91
references: 3897795
references: J Biol Chem. 1994 Nov 11;269(45):28259-62
references: 7961763
references: Biochemistry. 1995 Apr 11;34(14):4577-82
references: 7718559
references: Science. 1996 Jun 14;272(5268):1646-9
references: 8658138
references: Genetics. 1997 Dec;147(4):1557-68
references: 9409821
references: J Biol Chem. 1998 Feb 27;273(9):5412-8
references: 9479003
references: Genes Dev. 1998 Oct 1;12(19):3137-43
references: 9765213
references: Science. 1999 Feb 12;283(5404):1001-4
references: 9974380
references: Cell. 1999 Mar 5;96(5):645-53
references: 10089880
references: Nature. 1999 Jun 17;399(6737):700-4
references: 10385124
references: Science. 1999 Jul 9;285(5425):263-5
references: 10398605
references: Annu Rev Biochem. 2005;74:317-53
references: 15952890
references: Mol Cell Biol. 2005 Aug;25(16):7137-43
references: 16055723
references: Mol Cell Biol. 2005 Oct;25(19):8748-54
references: 16166652
references: Structure. 2005 Oct;13(10):1569-77
references: 16216587
references: Mol Cell Biol. 2006 Jan;26(1):381-6
references: 16354708
references: Structure. 2006 Apr;14(4):749-55
references: 16615915
references: Nat Struct Mol Biol. 2006 Jul;13(7):619-25
references: 16819516
references: Mol Cell Biol. 2006 Sep;26(17):6435-41
references: 16914729
references: Mol Cell Biol. 2006 Oct;26(20):7783-90
references: 16908531
references: Mol Cell. 2007 Feb 23;25(4):601-14
references: 17317631
references: Genes Dev. 2002 Aug 1;16(15):1872-83
references: 12154119
references: J Am Chem Soc. 2002 Aug 14;124(32):9324-5
references: 12166998
references: Nature. 2002 Sep 12;419(6903):135-41
references: 12226657
references: Genes Dev. 2003 Jan 1;17(1):77-87
references: 12514101
references: Mol Cell Biol. 2004 Jul;24(13):5687-93
references: 15199127
references: Nature. 2004 Jul 15;430(6997):377-80
references: 15254543
references: Biochem J. 1975 Jan;145(1):73-84
references: 172066
references: J Mol Biol. 1976 Mar 5;101(3):417-25
references: 1255724
references: Genetics. 1979 Jun;92(2):397-408
references: 385449
references: Methods Enzymol. 1983;101:202-11
references: 6310324
references: Gene. 1983 Sep;24(1):1-14
references: 6313478
references: Mutat Res. 1985 Jun-Jul;150(1-2):77-84
references: 4000169
references: J Biol Chem. 2003 Jan 10;278(2):784-90
references: 12401796
references: J Am Chem Soc. 2003 Jan 8;125(1):50-61
references: 12515506
references: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5113-8
references: 12692307
references: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3094-9
references: 10725365