Involvement of Schizosaccharomyces pombe Srs2 in cellular responses to DNA damage.

Journal article

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: Wang, S; Goodwin, A; Hickson, I; Norbury, C

• Publication status: Published
• Journal: Nucleic acids research
• Volume: 29
• Issue: 14
• Pages: 2963-2972
• Publication date: 2001-07-01
• DOI: 10.1093/nar/29.14.2963
• EISSN: 1362-4962
• ISSN: 0305-1048
• Language: English
• Keywords: Phenotype; Cell Division; DNA Topoisomerases, Type I; Gene Expression Regulation, Fungal; Gene Deletion; DNA Damage; Gene Expression Regulation, Enzymologic; DNA Repair; DNA-Binding Proteins; Sequence Homology, Amino Acid; Fungal Proteins; Hydroxyurea; Amino Acid Sequence; Saccharomyces cerevisiae Proteins; Schizosaccharomyces; Molecular Sequence Data; Recombination, Genetic; Rad51 Recombinase; DNA Helicases; Schizosaccharomyces pombe Proteins; Genes, Lethal; Ultraviolet Rays