The Escherichia coli gene recQ was identified as a RecF recombination pathway gene1. The gene SGS1, encoding the only RecQ-like DNA helicase in Saccharomyces cerevisiae, was identified by mutations that suppress the top3 slow-growth phenotype2,3. Relatively little is known about the function of Sgs1p because single mutations in SGS1 do not generally cause strong phenotypes. Mutations in genes encoding RecQ-like DNA helicases such as the Bloom and Werner syndrome genes, BLM and WRN, have been suggested to cause increased genome instability4,5. But the exact DNA metabolic defect that might underlie such genome instability has remained unclear. To better understand the cellular role of the RecQ-like DNA helicases, sgs1 mutations were analyzed for their effect on genome rearrangements6,7. Mutations in SGS1 increased the rate of accumulating gross chromosomal rearrangements (GCRs), including translocations and deletions containing extended regions of imperfect homology at their breakpoints. sgs1 mutations also increased the rate of recombination between DNA sequences that had 91% sequence homology. Epistasis analysis showed that Sgs1p is redundant with DNA mismatch repair (MMR) for suppressing GCRs and for suppressing recombination between divergent DNA sequences. This suggests that defects in the suppression of rearrangements involving divergent, repeated sequences may underlie the genome instability seen in BLM and WRN patients and in cancer cases associated with defects in these genes.
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Nakayama, H. et al. Isolation and genetic characterization of a thymineless death-resistant mutant of Escherichia coli K12: identification of a new mutation (recQ1) that blocks the RecF recombination pathway. Mol. Gen. Genet. 195, 475–480 (1984).
Gangloff, S., McDonald, J.P., Bendixen, C., Arthur, L. & Rothstein, R. The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol. Cell. Biol. 14, 8391–8398 (1994).
Bennett, R.J., Sharp, J.A. & Wang, J.C. Purification and characterization of the Sgs1 DNA helicase activity of Saccharomyces cerevisiae. J. Biol. Chem. 273, 9644–9650 (1998).
German, J. & Ellis, N.A. The Genetic Basis of Human Cancer 301–315 (McGraw-Hill, New York, 1998).
Moser, M.J., Shima, J. & Monnat, R.J. Jr., WRN mutations in Werner syndrome. Hum. Mut. 13, 271–279 (1999).
Chen, C., Umezu, K. & Kolodner, R.D. Chromosomal rearrangements occur in S. cerevisiae rfa1 mutator mutants due to mutagenic lesions processed by double-strand-break repair. Mol. Cell 2, 9–22 (1998).
Chen, C. & Kolodner, R.D. Gross chromosomal rearrangements in Saccharomyces cerevisiae replication and recombination defective mutants. Nature Genet. 23, 81–85 (1999).
Watt, P.M., Hickson, I.D., Borts, R.H. & Louis, E.J. SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics 144, 935–945 (1996).
Ng, S., Liu, Y., Hasselblatt, K.T., Mok, S.C. & Berkowitz, R.S. A new human topoisomerase III that interacts with SGS1 protein. Nucleic Acids Res. 27, 993–1000 (1999).
Datta, A., Adjiri, A., New, L., Crouse, G.F. & Jinks-Robertson, S. Mitotic crossovers between diverged sequences are regulated by mismatch repair proteins in Saccharomyces cerevisiae. Mol. Cell. Biol. 16, 1085–1093 (1996).
Matic, I., Rayssiguier, C. & Radman, M. Interspecies gene exchange in bacteria: the role of SOS and mismatch repair systems in evolution of species. Cell 80, 507–515 (1995).
Yamagata, K. et al. Bloom's and Werner's syndrome genes suppress hyperrecombination in yeast sgs1 mutant: implication for genomic instability in human diseases. Proc. Natl. Acad. Sci. USA 95, 8733–8738 (1998).
Nicholson, A., Hendrix, M., Jinks-Robertson, S. & Crouse, G.F. Regulation of mitotic homeologous recombination in yeast. Functions of mismatch repair and nucleotide excision repair genes. Genetics 154, 133–146 (2000).
Harmon, F.G. & Kowalczykowski, S.C. RecQ helicase, in concert with RecA and SSB proteins, initiates and disrupts DNA recombination. Genes Dev. 12, 1134–1144 (1998).
Gangloff, S., Soustelle, C. & Fabre, F. Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases. Nature Genet. 25, 192–194 (2000).
Frei, C. & Gasser, S.M. The yeast Sgs1p helicase acts upstream of Rad53p in the DNA replication checkpoint and colocalizes with Rad53p in S-phase-specific foci. Genes Dev. 14, 81–96 (2000).
Davey, S. et al. Fission yeast rad12+ regulates cell cycle checkpoint control and is homologous to the Bloom's syndrome disease gene. Mol. Cell. Biol. 18, 2721–2728 (1998).
Yan, H., Chen, C.Y., Kobayashi, R. & Newport, J. Replication focus-forming activity 1 and the Werner syndrome gene product. Nature Genet. 19, 375–378 (1998).
Blander, G. et al. Physical and functional interaction between p53 and the Werner's syndrome protein. J. Biol. Chem. 274, 29463–29469 (1999).
Schulz, V.P. & Zakian, V.A. The Saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation. Cell 76, 145–155 (1994).
Ellis, N.A. et al. The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 83, 655–666 (1995).
Yu, C.-E. et al. Positional cloning of the Werner's syndrome gene. Science 272, 258–262 (1996).
Goto, M., Miller, R.W., Ishikawa, Y. & Sugano, H. Excess of rare cancers in Werner syndrome (adult progeria). Cancer Epidemiol. Biomarkers Prev. 5, 239–246 (1996).
Shiraishi, Y., Kubonishi, I. & Sandberg, A.A. Establishment of B-lymphoid cell lines retaining cytogenetic characteristics of Bloom syndrome. Cancer Genet. Cytogenet. 9, 129–138 (1983).
Salk, D., Au, K., Hoehn, H. & Martin, G.M. Cytogenetic aspects of Werner syndrome. Adv. Exp. Med. Biol. 190, 541–546 (1985).
Fukuchi, K.-i. et al. Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients. Hum. Genet. 84, 249–252 (1990).
Monnat, R.J.J., Hackmann, A.F.M. & Chiaverotti, T.A. Nucleotide sequence analysis of human hypoxanthine phosphoribosyltransferase (HPRT) gene deletions. Genomics 13, 777–787 (1992).
Langlois, R.G., Bigbee, W.L., Jensen, R.H. & German, J. Evidence for increased in vivo mutation and somatic recombination in Bloom's syndrome. Proc. Natl. Acd. Sci. USA 86, 670–674 (1989).
Hanada, K. et al. RecQ DNA helicase is a suppressor of illegitimate recombination in Escherichia coli. Proc. Natl. Acad. Sci. USA 94, 3860–3865 (1997).
Calin, G., Herlea, V., Barbanti-Brodano, G. & Negrini, M. The coding region of the Bloom syndrome BLM gene and of the CBL proto-oncogene is mutated in genetically unstable sporadic gastrointestinal tumors. Cancer Res. 58, 3777–3781 (1998).
We thank S. Jinks-Robertson for the plasmids used in constructing the strains required for the recombination assays; A. Shoemaker, T. Nakagawa and J. Schmeits for discussions; J. Weger and J. Green for DNA sequencing; and R. Fishel for comments on the manuscript. This work was supported by National Institutes of Health grants GM26017 and GM50006 to R.D.K., a fellowship from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation to K.M. and a fellowship from the American Cancer Society to A.D.
About this article
Cite this article
Myung, K., Datta, A., Chen, C. et al. SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination. Nat Genet 27, 113–116 (2001) doi:10.1038/83673
Current Genetics (2019)
Mismatch recognition and subsequent processing have distinct effects on mitotic recombination intermediates and outcomes in yeast
Nucleic Acids Research (2019)