title: The Saccharomyces cerevisiae chromatin remodeler Fun30 regulates DNA end resection and checkpoint deactivation.
abstract: Fun30 is a Swi2/Snf2 homolog in budding yeast that has been shown to remodel chromatin both in vitro and in vivo. We report that Fun30 plays a key role in homologous recombination, by facilitating 5'-to-3' resection of double-strand break (DSB) ends, apparently by facilitating exonuclease digestion of nucleosome-bound DNA adjacent to the DSB. Fun30 is recruited to an HO endonuclease-induced DSB and acts in both the Exo1-dependent and Sgs1-dependent resection pathways. Deletion of FUN30 slows the rate of 5'-to-3' resection from 4 kb/h to about 1.2 kb/h. We also found that the resection rate is reduced by DNA damage-induced phosphorylation of histone H2A-S129 (γ-H2AX) and that Fun30 interacts preferentially with nucleosomes in which H2A-S129 is not phosphorylated. Fun30 is not required for later steps in homologous recombination. Like its homolog Rdh54/Tid1, Fun30 is required to allow the adaptation of DNA damage checkpoint-arrested cells with an unrepaired DSB to resume cell cycle progression.
authors.affiliation: Department of Biology, Rosenstiel Basic Medical Sciences Center, Brandeis University, Waltham, Massachusetts, USA.
authors.forename: Vinay V
authors.initials: VV
authors.lastname: Eapen
authors.forename: Neal
authors.initials: N
authors.lastname: Sugawara
authors.forename: Michael
authors.initials: M
authors.lastname: Tsabar
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Wu
authors.forename: James E
authors.initials: JE
authors.lastname: Haber
mesh_terms: D000222:Adaptation, Physiological; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D053903:DNA Breaks, Double-Stranded; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D004271:DNA, Fungal; C074000:FUN30 protein, S cerevisiae; D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases