title: Rad8Rad5/Mms2-Ubc13 ubiquitin ligase complex controls translesion synthesis in fission yeast.
abstract: Many DNA lesions cause pausing of replication forks at lesion sites; thus, generating gaps in the daughter strands that are filled-in by post-replication repair (PRR) pathways. In Saccharomyces cerevisiae, PRR involves translesion synthesis (TLS) mediated by Poleta or Polzeta, or Rad5-dependent gap filling through a poorly characterized error-free mechanism. We have developed an assay to monitor error-free and mutagenic TLS across single DNA lesions in Schizosaccharomyces pombe. For both main UV photolesions, we have delineated a major error-free pathway mediated by a distinct combination of TLS polymerases. Surprisingly, these TLS pathways require enzymes needed for poly-ubiquitination of proliferating cell nuclear antigen (PCNA) as well as those required for mono-ubiquitination. For pathways that require several TLS polymerases the poly-ubiquitin chains of PCNA may facilitate their recruitment through specific interactions with their multiple ubiquitin-binding motifs. These error-free TLS pathways may at least partially account for the previously described poly-ubiquitination-dependent error-free branch of PRR. This work highlights major differences in the control of lesion tolerance pathways between S. pombe and S. cerevisiae despite the homologous sets of PRR genes these organisms share.
authors.affiliation: CNRS, UPR 3081, Genome Instability and Carcinogenesis, Conventionné par l'Université d'Aix-Marseille 2, Marseille cedex 20, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Coulon
authors.forename: Sharada
authors.initials: S
authors.lastname: Ramasubramanyan
authors.forename: Carole
authors.initials: C
authors.lastname: Alies
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Philippin
authors.forename: Alan
authors.initials: A
authors.lastname: Lehmann
authors.forename: Robert P
authors.initials: RP
authors.lastname: Fuchs
mesh_terms: D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism* / Q000528:radiation effects; D046911:Macromolecular Substances; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D004271:DNA, Fungal; D046911:Macromolecular Substances; D029702:Schizosaccharomyces pombe Proteins; C513353:Mms2 protein, S pombe; C513352:Ubc13 protein, S pombe; D044763:Ubiquitin-Conjugating Enzymes; D004265:DNA Helicases
references.citation: Yeast. 1998 Jul;14(10):943-51
references.pmid: 9717240
references.citation: EMBO J. 2009 Aug 19;28(16):2307-8
references.pmid: 19690555
references.citation: EMBO J. 2004 Oct 1;23(19):3886-96
references.pmid: 15359278
references.citation: Mol Cell. 2006 Jan 6;21(1):15-27
references.pmid: 16387650
references.citation: DNA Repair (Amst). 2008 Oct 1;7(10):1636-46
references.pmid: 18634905
references.citation: Science. 1996 Jun 14;272(5268):1646-9
references.pmid: 8658138
references.citation: Cell. 2007 May 18;129(4):665-79
references.pmid: 17512402
references.citation: Yeast. 2001 Aug;18(11):1015-21
references.pmid: 11481672
references.citation: Mol Cell Biol. 2006 Oct;26(20):7783-90
references.pmid: 16908531
references.citation: Nucleic Acids Res. 2005 Aug 24;33(15):4762-74
references.pmid: 16120966
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15954-9
references.pmid: 16247017
references.citation: EMBO J. 2002 Jul 15;21(14):3881-7
references.pmid: 12110599
references.citation: Methods Enzymol. 1991;194:795-823
references.pmid: 2005825
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18219-24
references.pmid: 19822754
references.citation: Mol Biol Cell. 2006 Jul;17(7):2976-85
references.pmid: 16641370
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18361-6
references.pmid: 16344468
references.citation: Mutat Res. 1993 May;299(3-4):157-63
references.pmid: 7683084
references.citation: Proc Natl Acad Sci U S A. 1989 Jun;86(11):4147-51
references.pmid: 2657743
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11552-7
references.pmid: 19564618
references.citation: Yeast. 2005 May;22(7):583-91
references.pmid: 15942936
references.citation: EMBO J. 2000 Jun 15;19(12):3100-9
references.pmid: 10856253
references.citation: Nature. 2002 Sep 12;419(6903):135-41
references.pmid: 12226657
references.citation: Proc Natl Acad Sci U S A. 1975 Jan;72(1):219-23
references.pmid: 1054497
references.citation: Mol Cell. 2005 May 27;18(5):499-505
references.pmid: 15916957
references.citation: Mol Cell Biol. 2006 Dec;26(23):8892-900
references.pmid: 16982685
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5361-6
references.pmid: 18385374
references.citation: Nature. 2003 Sep 11;425(6954):188-91
references.pmid: 12968183
references.citation: Mol Gen Genet. 1982;187(2):326-9
references.pmid: 6294466
references.citation: Genes Cells. 2003 May;8(5):437-49
references.pmid: 12694533
references.citation: EMBO J. 2009 Aug 19;28(16):2461-8
references.pmid: 19536136
references.citation: EMBO J. 2009 Dec 2;28(23):3657-66
references.pmid: 19851286
references.citation: Mol Cell Biol. 2001 May;21(10):3558-63
references.pmid: 11313481
references.citation: Nat Rev Mol Cell Biol. 2009 Nov;10(11):755-64
references.pmid: 19851334
references.citation: J Biol Chem. 2004 May 14;279(20):21543-51
references.pmid: 15014081
references.citation: Genetics. 2005 Feb;169(2):575-82
references.pmid: 15520252
references.citation: Mol Cell. 2001 Jul;8(1):7-8
references.pmid: 11515498
references.citation: EMBO J. 2009 Feb 18;28(4):383-93
references.pmid: 19153606
references.citation: Mol Cell. 2004 May 21;14(4):491-500
references.pmid: 15149598
references.citation: Annu Rev Biochem. 2005;74:317-53
references.pmid: 15952890
references.citation: Gene. 1995 Oct 16;164(1):173-7
references.pmid: 7590311
references.citation: Science. 1999 Jul 9;285(5425):263-5
references.pmid: 10398605
references.citation: Nature. 1999 Jun 17;399(6737):700-4
references.pmid: 10385124
references.citation: Science. 2003 May 23;300(5623):1300-3
references.pmid: 12764199
references.citation: Genetics. 2008 Sep;180(1):73-82
references.pmid: 18757916
references.citation: EMBO J. 2006 Jun 21;25(12):2847-55
references.pmid: 16763556
references.citation: J Mol Biol. 1999 Nov 26;294(2):299-306
references.pmid: 10610759
references.citation: Science. 2005 Dec 16;310(5755):1821-4
references.pmid: 16357261