title: Histone H3 K79 methylation states play distinct roles in UV-induced sister chromatid exchange and cell cycle checkpoint arrest in Saccharomyces cerevisiae.
abstract: Histone post-translational modifications have been shown to contribute to DNA damage repair. Prior studies have suggested that specific H3K79 methylation states play distinct roles in the response to UV-induced DNA damage. To evaluate these observations, we examined the effect of altered H3K79 methylation patterns on UV-induced G1/S checkpoint response and sister chromatid exchange (SCE). We found that the di- and trimethylated states both contribute to activation of the G1/S checkpoint to varying degrees, depending on the synchronization method, although methylation is not required for checkpoint in response to high levels of UV damage. In contrast, UV-induced SCE is largely a product of the trimethylated state, which influences the usage of gene conversion versus popout mechanisms. Regulation of H3K79 methylation by H2BK123 ubiquitylation is important for both checkpoint function and SCE. H3K79 methylation is not required for the repair of double-stranded breaks caused by transient HO endonuclease expression, but does play a modest role in survival from continuous exposure. The overall results provide evidence for the participation of H3K79 methylation in UV-induced recombination repair and checkpoint activation, and further indicate that the di- and trimethylation states play distinct roles in these DNA damage response pathways.
authors.affiliation: Department of Biology, Denison University, Granville, OH 43023, USA.
authors.forename: Alyssa A
authors.initials: AA
authors.lastname: Rossodivita
authors.affiliation: Department of Biology, Denison University, Granville, OH 43023, USA.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Boudoures
authors.affiliation: Department of Biology, Denison University, Granville, OH 43023, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Mecoli
authors.affiliation: Department of Biology, Denison University, Granville, OH 43023, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Steenkiste
authors.affiliation: Department of Biology, Denison University, Granville, OH 43023, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Karl
authors.affiliation: Department of Biology, Denison University, Granville, OH 43023, USA.
authors.forename: Eudora M
authors.initials: EM
authors.lastname: Vines
authors.affiliation: Department of Biology, Denison University, Granville, OH 43023, USA.
authors.forename: Arron M
authors.initials: AM
authors.lastname: Cole
authors.affiliation: Department of Biology, Denison University, Granville, OH 43023, USA.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Ansbro
authors.affiliation: Department of Biology, Denison University, Granville, OH 43023, USA thompsonjs@denison.edu.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Thompson
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D059585:G1 Phase Cell Cycle Checkpoints / Q000528:radiation effects*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006918:Hydroxyurea / Q000633:toxicity; D008745:Methylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D012854:Sister Chromatid Exchange; D054875:Ubiquitination; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D006657:Histones; D006918:Hydroxyurea
references.citation: Nature. 2002 Jul 4;418(6893):104-8
references.pmid: 12077605
references.citation: Mol Cell. 2005 Jul 22;19(2):271-7
references.pmid: 16039595
references.citation: Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7985-9
references.pmid: 8367452
references.citation: J Biol Chem. 2002 Sep 20;277(38):34655-7
references.pmid: 12167634
references.citation: Genetics. 2012 May;191(1):33-64
references.pmid: 22555442
references.citation: Mol Cell. 2007 Oct 12;28(1):167-75
references.pmid: 17936713
references.citation: EMBO J. 1998 May 1;17(9):2687-98
references.pmid: 9564050
references.citation: Methods Enzymol. 1991;194:132-46
references.pmid: 2005783
references.citation: J Biol Chem. 2005 Mar 18;280(11):9879-86
references.pmid: 15632126
references.citation: Yeast. 1998 Jan 30;14(2):115-32
references.pmid: 9483801
references.citation: EMBO J. 2005 Jun 1;24(11):1999-2010
references.pmid: 15902273
references.citation: Nat Rev Mol Cell Biol. 2005 Oct;6(10):757-65
references.pmid: 16167054
references.citation: Epigenetics Chromatin. 2008 Nov 12;1(1):9
references.pmid: 19014481
references.citation: DNA Repair (Amst). 2006 Jun 10;5(6):693-703
references.pmid: 16650810
references.citation: Mol Cell Biol. 2005 Oct;25(19):8430-43
references.pmid: 16166626
references.citation: DNA Repair (Amst). 2005 Jul 28;4(8):855-69
references.pmid: 15925550
references.citation: Nucleic Acids Res. 2011 Sep 1;39(16):7049-57
references.pmid: 21646340
references.citation: Curr Genet. 2008 May;53(5):259-74
references.pmid: 18327589
references.citation: Genetics. 2005 Jan;169(1):51-63
references.pmid: 15371366
references.citation: Mol Cell Biol. 1992 Sep;12(9):3807-18
references.pmid: 1324406
references.citation: Genetics. 2008 Jan;178(1):113-26
references.pmid: 18202362
references.citation: Mutat Res. 2001 Jul 12;486(2):137-46
references.pmid: 11425518
references.citation: Genetics. 2006 Aug;173(4):1951-68
references.pmid: 16783014
references.citation: Genetics. 2009 Jun;182(2):437-46
references.pmid: 19332880
references.citation: J Genet. 1949 Dec;49(3):264-85
references.pmid: 24536673
references.citation: Mutat Res. 2008 Dec 15;648(1-2):73-81
references.pmid: 18929581
references.citation: EMBO J. 2008 May 21;27(10):1502-12
references.pmid: 18418382
references.citation: Mol Cell. 2009 Sep 11;35(5):626-41
references.pmid: 19682934
references.citation: Genetics. 2008 Jul;179(3):1197-210
references.pmid: 18562671
references.citation: Cell Cycle. 2014;13(5):726-38
references.pmid: 24526115
references.citation: Methods Mol Biol. 2004;262:3-12
references.pmid: 14769952
references.citation: Cell. 2002 Jun 14;109(6):745-56
references.pmid: 12086673
references.citation: Nature. 2009 Oct 22;461(7267):1071-8
references.pmid: 19847258
references.citation: J Cell Biol. 2009 Aug 10;186(3):371-7
references.pmid: 19667127
references.citation: DNA Repair (Amst). 2007 Mar 1;6(3):383-95
references.pmid: 17267293
references.citation: PLoS One. 2011;6(10):e26210
references.pmid: 22053185
references.citation: Nature. 1994 May 19;369(6477):245-7
references.pmid: 8183346
references.citation: Genes Dev. 2002 Jun 15;16(12):1518-27
references.pmid: 12080090
references.citation: J Biol Chem. 2011 May 20;286(20):17530-5
references.pmid: 21460225
references.citation: Mol Cell Biol. 2004 Dec;24(23):10180-92
references.pmid: 15542829
references.citation: Nucleic Acids Res. 2009 Apr;37(5):1690-700
references.pmid: 19155276
references.citation: Genetics. 2003 Jan;163(1):447-52
references.pmid: 12586729
references.citation: Genetics. 1993 Mar;133(3):469-87
references.pmid: 8454200
references.citation: Nature. 2004 Nov 18;432(7015):406-11
references.pmid: 15525939
references.citation: Mol Cell Biol. 2007 Nov;27(21):7758-64
references.pmid: 17785441
references.citation: Mutat Res. 2000 Jun 30;451(1-2):13-24
references.pmid: 10915862
references.citation: Mutat Res. 2000 Jun 30;451(1-2):91-105
references.pmid: 10915867