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PMID: 11452021 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nucleic acids research ·Vol. 29 ·No. 14 ·2001-07-15 ·Pages 2963-72

Wang SW, Goodwin A, Hickson ID, Norbury CJ

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.

MeSH Terms
Amino Acid Sequence Cell Division/drug effects,genetics,radiation effects DNA Damage DNA Helicases/genetics,metabolism DNA Repair DNA Topoisomerases, Type I/genetics DNA-Binding Proteins Fungal Proteins/genetics Gene Deletion Gene Expression Regulation, Enzymologic Gene Expression Regulation, Fungal Genes, Lethal Hydroxyurea/pharmacology Molecular Sequence Data Phenotype Rad51 Recombinase Recombination, Genetic Saccharomyces cerevisiae Proteins Schizosaccharomyces/enzymology,genetics Schizosaccharomyces pombe Proteins Sequence Homology, Amino Acid Ultraviolet Rays
Chemicals
DNA-Binding Proteins Fungal Proteins RHP51 protein, S pombe Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins SRS2 protein, S cerevisiae Rad51 Recombinase DNA Helicases Rqh1 protein, S pombe DNA Topoisomerases, Type I Hydroxyurea
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Wang S W
Imperial Cancer Research Fund Molecular Oncology Laboratory, University of Oxford Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Goodwin A
Hickson I D
Norbury C J
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
Published
2001-07-15
Pages
2963-72
Language
English
Region
England
NLM ID
0411011
PMCID
PMC55813
Subset
IM
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