title: RSC functions as an early double-strand-break sensor in the cell's response to DNA damage.
abstract: The detection of a DNA double-strand break (DSB) is necessary to initiate DSB repair. Several proteins, including the MRX/N complex, Tel1/ATM (ataxia telangiectasia mutated), and Mec1/ATR (ATM and Rad3 related), have been proposed as sensors of DNA damage, yet how they recognize the breaks is poorly understood. DSBs occur in the context of chromatin, implicating factors capable of altering local and/or global chromatin structure in the cellular response to DNA damage, including DSB sensing. Emerging evidence indicates that ATP-dependent chromatin-remodeling complexes function in DNA repair. Here we describe an important and novel early role for the RSC ATP-dependent chromatin remodeler linked to DSB sensing in the cell's DNA-damage response. RSC is required for full levels of H2A phosphorylation because it facilitates the recruitment of Tel1/ATM and Mec1/ATR to the break site. Consistent with these results, we also show that Rsc2 is needed for efficient activation of the Rad53-dependent checkpoint, as well as for Cohesin's association with the break site. Finally, Rsc2 is needed for the DNA-damage-induced changes in nucleosome structure surrounding the DSB site. Together, these new findings functionally link RSC to DSB sensing, highlighting the importance of ATP-dependent chromatin-remodeling factors in the cell's early response to DNA damage.
authors: Department of Oncological Sciences, One Gustave L. Levy Place, Box 1130, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors: Bing
authors: B
authors: Liang
authors: Jiajing
authors: J
authors: Qiu
authors: Kajan
authors: K
authors: Ratnakumar
authors: Brehon C
authors: BC
authors: Laurent
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000097722:Cohesins; C103337:RSC complex, S cerevisiae; C069930:rad9 protein
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