title: Functions of Fun30 chromatin remodeler in regulating cellular resistance to genotoxic stress.
abstract: The Saccharomyces cerevisiae Fun30 chromatin remodeler has recently been shown to facilitate long-range resection of DNA double strand break (DSB) ends, which proceeds homologous recombination (HR). This is believed to underlie the role of Fun30 in promoting cellular resistance to DSB inducing agent camptothecin. We show here that Fun30 also contributes to cellular resistance to genotoxins methyl methanesulfonate (MMS) and hydroxyurea (HU) that can stall the progression of DNA replication. We present evidence implicating DNA end resection in Fun30-dependent MMS-resistance. On the other hand, we show that Fun30 deletion suppresses the MMS- and HU-sensitivity of cells lacking the Rad5/Mms2/Ubc13-dependent error-free DNA damage tolerance mechanism. This suppression is not the result of a reduction in DNA end resection, and is dependent on the key HR component Rad51. We further show that Fun30 negatively regulates the recovery of rad5Δ mutant from MMS induced G2/M arrest. Therefore, Fun30 has two functions in DNA damage repair: one is the promotion of cellular resistance to genotoxic stress by aiding in DNA end resection, and the other is the negative regulation of a Rad51-dependent, DNA end resection-independent mechanism for countering replicative stress. The latter becomes manifest when Rad5 dependent DNA damage tolerance is impaired. In addition, we find that the putative ubiquitin-binding CUE domain of Fun30 serves to restrict the ability of Fun30 to hinder MMS- and HU-tolerance in the absence of Rad5.
authors: Department of Biology, University of Rochester, Rochester, New York, United States of America.
authors: Xin
authors: X
authors: Bi
authors: Department of Biology, University of Rochester, Rochester, New York, United States of America.
authors: Qun
authors: Q
authors: Yu
authors: Department of Biology, University of Rochester, Rochester, New York, United States of America.
authors: Jasmine
authors: J
authors: Siler
authors: Department of Biology, University of Rochester, Rochester, New York, United States of America.
authors: Chong
authors: C
authors: Li
authors: Department of Biology, University of Rochester, Rochester, New York, United States of America.
authors: Ali
authors: A
authors: Khan
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D059765:Homologous Recombination / Q000235:genetics; D006918:Hydroxyurea / Q000633:toxicity; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004271:DNA, Fungal; C074000:FUN30 protein, S cerevisiae; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D008741:Methyl Methanesulfonate; D006918:Hydroxyurea