Genetics, Vol 144, 935-945, Copyright © 1996

INVESTIGATIONS

SGS1, a Homologue of the Bloom's and Werner's Syndrome Genes, Is Required for Maintenance of Genome Stability in Saccharomyces cerevisiae

P. M. Watt, I. D. Hickson, R. H. Borts and E. J. Louis
Imperial Cancer Research Fund Laboratories, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom Present address:Institute of Child Health Research, University of Western Australia, Perth 6008, Australia.

The Saccharomyces cerevisiae SGS1 gene is homologous to Escherichia coli RecQ and the human BLM and WRN proteins that are defective in the cancer-prone disorder Bloom's syndrome and the premature aging disorder Werner's syndrome, respectively. While recQ mutants are deficient in conjugational recombination and DNA repair, Bloom's syndrome cell lines show hyperrecombination. Bloom's and Werner's syndrome cell lines both exhibit chromosomal instability. sgs1{Delta} strains show mitotic hyperrecombination, as do Bloom's cells. This was manifested as an increase in the frequency of interchromosomal homologous recombination, intrachromosomal excision recombination, and ectopic recombination. Hyperrecombination was partially independent of both RAD52 and RAD1. Meiotic recombination was not increased in sgs1{Delta} mutants, although meiosis I chromosome missegregation has been shown to be elevated. sgs1{Delta} suppresses the slow growth of a top3{Delta} strain lacking topoisomerase III. Although there was an increase in subtelomeric Y' instability in sgs1{Delta} strains due to hyperrecombination, no evidence was found for an increase in the instability of terminal telomeric sequences in a top3{Delta} or a sgs1{Delta} strain. This contrasts with the telomere maintenance defects of Werner's patients. We conclude that the SGS1 gene product is involved in the maintenance of genome stability in S. cerevisiae.


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