title: Involvement of Schizosaccharomyces pombe Srs2 in cellular responses to DNA damage.
abstract: In the budding yeast Saccharomyces cerevisiae the Srs2/RadH DNA helicase promotes survival after ultraviolet (UV) irradiation, and has been implicated in DNA repair, recombination and checkpoint signalling following DNA damage. A second helicase, Sgs1, is the S.cerevisiae homologue of the human BLM and WRN proteins, which are defective in cancer predisposition and/or premature ageing syndromes. Saccharomyces cerevisiae cells lacking both Srs2 and Sgs1 exhibit a severe growth defect. We have identified an Srs2 orthologue in the fission yeast Schizosaccharomyces pombe, and have investigated its role in responses to UV irradiation and inhibition of DNA replication. Deletion of fission yeast srs2 caused spontaneous hyper-recombination and UV sensitivity, and simultaneous deletion of the SGS1 homologue rqh1 caused a severe growth defect reminiscent of that seen in the equivalent S.cerevisiae mutant. However, unlike in budding yeast, inactivation of the homologous recombination pathway did not suppress this growth defect. Indeed, the homologous recombination pathway was required for maintenance of normal fission yeast viability in the absence of Srs2, and loss of homologous recombination and loss of Srs2 contributed additively to UV sensitivity. We conclude that Srs2 plays related, but not identical, roles in the two yeast species.
authors.affiliation: Imperial Cancer Research Fund Molecular Oncology Laboratory, University of Oxford Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK.
authors.forename: S W
authors.initials: SW
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Goodwin
authors.forename: I D
authors.initials: ID
authors.lastname: Hickson
authors.forename: C J
authors.initials: CJ
authors.lastname: Norbury
mesh_terms: D000595:Amino Acid Sequence; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D005804:Genes, Lethal; D006918:Hydroxyurea / Q000494:pharmacology; D008969:Molecular Sequence Data; D010641:Phenotype; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D014466:Ultraviolet Rays
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C084232:RHP51 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C061376:SRS2 protein, S cerevisiae; D051135:Rad51 Recombinase; D004265:DNA Helicases; C106462:Rqh1 protein, S pombe; D004264:DNA Topoisomerases, Type I; D006918:Hydroxyurea