title: Fission yeast Ku protein is required for recovery from DNA replication stress.
abstract: The fundamental function of the conserved Ku70-Ku80 heterodimer is to promote the non-homologous end-joining (NHEJ) pathway in double-strand break repair. Although it is thought that Ku plays several roles other than NHEJ in maintaining chromosomal integrity including telomere protection, these precise functions remain unclear. In this study, we describe a novel role of fission yeast Ku proteins encoded by pku70(+) and pku80(+) genes in dealing with DNA replication stress. In the absence of Rqh1, the fission yeast RecQ helicase, the cells are sensitive to reagents inducing replication stress. pkuDeltarqh1Delta double mutant showed synergistic sensitivities to these reagents. However, this synthetic phenotype was not observed when rqh1Delta mutant was coupled with the deletion of lig4(+) that encodes a ligase essential for NHEJ, indicating that the role of Ku in replication stress is NHEJ independent. pkuDeltarqh1Delta double mutant also showed highly variable copy numbers of rDNA repeats even under unstressed condition. Furthermore, the double mutant exhibited inefficient replication resumption after transient replication stalling. These results suggest the possibility that Ku proteins play an important role in genome integrity recovering replication stress.
authors.affiliation: Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Junko
authors.initials: J
authors.lastname: Kanoh
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Ishikawa
mesh_terms: D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D018869:Heat-Shock Response; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C508551:NHEJ1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C081647:high affinity DNA-binding factor, S cerevisiae; D004265:DNA Helicases; C106462:Rqh1 protein, S pombe; D045643:DNA Repair Enzymes