title: The SWI/SNF ATP-dependent nucleosome remodeler promotes resection initiation at a DNA double-strand break in yeast.
abstract: DNA double-strand breaks (DSBs) are repaired by either the non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Pathway choice is determined by the generation of 3΄ single-strand DNA overhangs at the break that are initiated by the action of the Mre11-Rad50-Xrs2 (MRX) complex to direct repair toward HR. DSB repair occurs in the context of chromatin, and multiple chromatin regulators have been shown to play important roles in the repair process. We have investigated the role of the SWI/SNF ATP-dependent nucleosome-remodeling complex in the repair of a defined DNA DSB. SWI/SNF was previously shown to regulate presynaptic events in HR, but its function in these events is unknown. We find that in the absence of functional SWI/SNF, the initiation of DNA end resection is significantly delayed. The delay in resection initiation is accompanied by impaired recruitment of MRX to the DSB, and other functions of MRX in HR including the recruitment of long-range resection factors and activation of the DNA damage response are also diminished. These phenotypes are correlated with a delay in the eviction of nucleosomes surrounding the DSB. We propose that SWI/SNF orchestrates the recruitment of a pool of MRX that is specifically dedicated to HR.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.|Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
authors.forename: Nathaniel E
authors.initials: NE
authors.lastname: Wiest
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Houghtaling
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Sanchez
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.|Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Tomkinson
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Osley
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000378:metabolism / Q000494:pharmacology; D009707:Nucleosomes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D059767:Recombinational DNA Repair; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009707:Nucleosomes; C086930:RAD50 protein, S cerevisiae; C445179:SWI-SNF-B chromatin-remodeling complex; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086929:XRS2 protein, S cerevisiae; D000255:Adenosine Triphosphate; D004247:DNA; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; D005690:Galactose