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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 Proc. Natl. Acad. Sci. USAHome page
T. Hishida, H. Iwasaki, T. Ohno, T. Morishita, and H. Shinagawa
A yeast gene, MGS1, encoding a DNA-dependent AAA+ ATPase is required to maintain genome stability
PNAS, July 17, 2001; 98(15): 8283 - 8289.
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 Proc. Natl. Acad. Sci. USAHome page
L. Davis and G. R. Smith
Meiotic recombination and chromosome segregation in Schizosaccharomyces pombe
PNAS, July 17, 2001; 98(15): 8395 - 8402.
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 Proc. Natl. Acad. Sci. USAHome page
K. M. Vasquez, K. Marburger, Z. Intody, and J. H. Wilson
Manipulating the mammalian genome by homologous recombination
PNAS, July 17, 2001; 98(15): 8403 - 8410.
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 Nucleic Acids ResHome page
S.-W. Wang, A. Goodwin, I. D. Hickson, and C. J. Norbury
Involvement of Schizosaccharomyces pombe Srs2 in cellular responses to DNA damage
Nucleic Acids Res., July 15, 2001; 29(14): 2963 - 2972.
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 Hum Mol GenetHome page
P. Hu, S. Beresten, A. van Brabant, T.-Z. Ye, P.-P. Pandolfi, F. B. Johnson, L. Guarente, and N. A. Ellis
Evidence for BLM and Topoisomerase III{{alpha}} interaction in genomic stability
Hum. Mol. Genet., June 1, 2001; 10(12): 1287 - 1298.
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 Proc. Natl. Acad. Sci. USAHome page
K. Y. Kwan and J. C. Wang
Mice lacking DNA topoisomerase IIIbeta develop to maturity but show a reduced mean lifespan
PNAS, April 25, 2001; (2001) 101132498.
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 Genes Dev.Home page
P. R. Prince, M. J. Emond, and R. J. Monnat Jr.
Loss of Werner syndrome protein function promotes aberrant mitotic recombination
Genes & Dev., April 15, 2001; 15(8): 933 - 938.
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 GeneticsHome page
M. McVey, M. Kaeberlein, H. A. Tissenbaum, and L. Guarente
The Short Life Span of Saccharomyces cerevisiae sgs1 and srs2 Mutants Is a Composite of Normal Aging Processes and Mitotic Arrest Due to Defective Recombination
Genetics, April 1, 2001; 157(4): 1531 - 1542.
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 Mol. Cell. Biol.Home page
L. Signon, A. Malkova, M. L. Naylor, H. Klein, and J. E. Haber
Genetic Requirements for RAD51- and RAD54-Independent Break-Induced Replication Repair of a Chromosomal Double-Strand Break
Mol. Cell. Biol., March 15, 2001; 21(6): 2048 - 2056.
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 Proc. Natl. Acad. Sci. USAHome page
H. Cohen and D. A. Sinclair
Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase
PNAS, March 1, 2001; (2001) 61579598.
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 GeneticsHome page
H. L. Klein
Mutations in Recombinational Repair and in Checkpoint Control Genes Suppress the Lethal Combination of srs2{{Delta}} With Other DNA Repair Genes in Saccharomyces cerevisiae
Genetics, February 1, 2001; 157(2): 557 - 565.
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 GeneticsHome page
J. R. Mullen, V. Kaliraman, S. S. Ibrahim, and S. J. Brill
Requirement for Three Novel Protein Complexes in the Absence of the Sgs1 DNA Helicase in Saccharomyces cerevisiae
Genetics, January 1, 2001; 157(1): 103 - 118.
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 Pharmacol. Rev.Home page
P. Perego, G. S. Jimenez, L. Gatti, S. B. Howell, and F. Zunino
Yeast Mutants As a Model System for Identification of Determinants of Chemosensitivity
Pharmacol. Rev., December 1, 2000; 52(4): 477 - 492.
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 Mol. Cell. Biol.Home page
A. Miyajima, M. Seki, F. Onoda, M. Shiratori, N. Odagiri, K. Ohta, Y. Kikuchi, Y. Ohno, and T. Enomoto
Sgs1 Helicase Activity Is Required for Mitotic but Apparently Not for Meiotic Functions
Mol. Cell. Biol., September 1, 2000; 20(17): 6399 - 6409.
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 GeneticsHome page
A. J. R. Bishop, E. J. Louis, and R. H. Borts
Minisatellite Variants Generated in Yeast Meiosis Involve DNA Removal During Gene Conversion
Genetics, September 1, 2000; 156(1): 7 - 20.
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 Proc. Natl. Acad. Sci. USAHome page
A. S. Kamath-Loeb, E. Johansson, P. M. J. Burgers, and L. A. Loeb
Functional interaction between the Werner Syndrome protein and DNA polymerase delta
PNAS, April 25, 2000; 97(9): 4603 - 4608.
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 J. Biol. Chem.Home page
L. Wu, S. L. Davies, P. S. North, H. Goulaouic, J.-F. Riou, H. Turley, K. C. Gatter, and I. D. Hickson
The Bloom's Syndrome Gene Product Interacts with Topoisomerase III
J. Biol. Chem., March 24, 2000; 275(13): 9636 - 9644.
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 GeneticsHome page
J. R. Mullen, V. Kaliraman, and S. J. Brill
Bipartite Structure of the SGS1 DNA Helicase in Saccharomyces cerevisiae
Genetics, March 1, 2000; 154(3): 1101 - 1114.
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 Nucleic Acids ResHome page
Y. Hirota and J. M. Lahti
Characterization of the enzymatic activity of hChlR1, a novel human DNA helicase
Nucleic Acids Res., February 15, 2000; 28(4): 917 - 924.
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 J. Biol. Chem.Home page
T. M. Wilson, A. D. Chen, and T.-s. Hsieh
Cloning and Characterization of Drosophila Topoisomerase IIIbeta . RELAXATION OF HYPERNEGATIVELY SUPERCOILED DNA
J. Biol. Chem., January 21, 2000; 275(3): 1533 - 1540.
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 J. Cell Sci.Home page
C Frei and S. Gasser
RecQ-like helicases: the DNA replication checkpoint connection
J. Cell Sci., January 8, 2000; 113(15): 2641 - 2646.
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 J. Cell Sci.Home page
P. Moens, R Freire, M Tarsounas, B Spyropoulos, and S. Jackson
Expression and nuclear localization of BLM, a chromosome stability protein mutated in Bloom's syndrome, suggest a role in recombination during meiotic prophase
J. Cell Sci., January 2, 2000; 113(4): 663 - 672.
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