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Gene Review

SGS1  -  Sgs1p

Saccharomyces cerevisiae S288c

Synonyms: ATP-dependent helicase SGS1, Helicase TPS1, TPS1, YM9646.02C, YMR190C
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Disease relevance of SGS1

  • All of these phenotypic consequences of loss of Top3p function are at least partially suppressed by deletion of SGS1, the yeast homologue of the human Bloom's and Werner's syndrome genes [1].
  • Late-generation sgs1 and srs2 cells senesce due to apparent premature aging, most likely involving the accumulation of extrachromosomal rDNA circles [2].
  • Mutation of SGS1 is shown to cause premature aging in yeast mother cells on the basis of a shortened life-span and the aging-induced phenotypes of sterility and redistribution of the Sir3 silencing protein from telomeres to the nucleolus [3].
  • In contrast, the SGS1 K(706)-->A allele was sufficient to rescue the hypersensitivity of the sgs1Delta strain to topoisomerase inhibitors, but not other genotoxic agents [4].
  • Sgs1: a eukaryotic homolog of E. coli RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation [5].

High impact information on SGS1

  • The resulting network predicts that the Mph1 helicase has a role in resolving homologous recombination-derived DNA intermediates that is similar to (but distinct from) that of the Sgs1 helicase [6].
  • We used SGS1 and SRS2, two 3'-->5' DNA helicase genes, as 'queries' to identify their redundant and unique biological functions [7].
  • Relatively little is known about the function of Sgs1p because single mutations in SGS1 do not generally cause strong phenotypes [8].
  • Epistasis analysis showed that Sgs1p is redundant with DNA mismatch repair (MMR) for suppressing GCRs and for suppressing recombination between divergent DNA sequences [8].
  • 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 [8].

Chemical compound and disease context of SGS1


Biological context of SGS1


Anatomical context of SGS1


Associations of SGS1 with chemical compounds

  • Disruption of SGS1 results in high sensitivity to methyl methanesulfonate (MMS), poor sporulation, and a hyper-recombination phenotype including recombination between heteroalleles [15].
  • Furthermore, we found that multiple copies of SGS1, a gene encoding a helicase that can unwind guanine quadruplexes, inhibited suppression of the cdc13-1 phenotype by STM1 [16].
  • In this study, we found that several amino acids residues in the N-terminal region of Sgs1 between residues 4 and 33 were responsible for binding to Top3 and essential for complementing the sensitivity to MMS of sgsl cells [17].
  • In this study, we examined whether Sgs1 prevents formation of DNA double strand breaks (DSBs) or is involved in DSB repair following exposure to methyl methanesulfonate (MMS) [18].
  • Disruption of the SGS1 gene is associated with high sensitivity to methyl methanesulfonate (MMS) and hydroxyurea (HU), and with hyper-recombination phenotypes, including interchromosomal recombination between heteroalleles [19].

Physical interactions of SGS1

  • We show that Rmi1 forms a heteromeric complex with Sgs1-Top3 in yeast and that these proteins interact directly in a recombinant system [10].
  • In this report, we show that yeast Mlh3 co-immunoprecipitates with Sgs1 helicase in sporulating cells at late stage of meiotic prophase I [20].
  • We have recently shown that Sgs1p interacts with the DNA repair Rad16p protein and is epistatic to Rad16p for UVC, 4-NQO and H2O2 lesions [21].
  • These results indicate that the 3' to 5' polarity of unwinding by the recombinant Sgs1 protein is a direct consequence of the binding of the helicase to the single-stranded/double-stranded DNA junction and its recognition of the polarity of the single-stranded DNA at the junction [22].

Regulatory relationships of SGS1

  • Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae [15].
  • Interestingly, an extra copy of YKU70 partially suppressed the increase in targeted integration seen in the sgs1 single mutant [23].
  • Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity [24].

Other interactions of SGS1

  • We present a model wherein Rad51 helps recruit Sgs1-Top3 to sites of replicative damage [25].
  • In this study, we found that SGS1 forms part of the RAD52 epistasis group when cells are exposed to MMS [15].
  • Replication fork bypass processes appear to be highly conserved within eukaryotes, with homologs for SGS1 and MGS1 found in both Schizosaccharomyces pombe and mammalian cells [26].
  • Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae [27].
  • Here, we report the isolation and characterization of temperature-sensitive (ts) SGS1 alleles in cells lacking SLX4 [28].

Analytical, diagnostic and therapeutic context of SGS1


  1. Topoisomerase III acts upstream of Rad53p in the S-phase DNA damage checkpoint. Chakraverty, R.K., Kearsey, J.M., Oakley, T.J., Grenon, M., de La Torre Ruiz, M.A., Lowndes, N.F., Hickson, I.D. Mol. Cell. Biol. (2001) [Pubmed]
  2. 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. McVey, M., Kaeberlein, M., Tissenbaum, H.A., Guarente, L. Genetics (2001) [Pubmed]
  3. Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants. Sinclair, D.A., Mills, K., Guarente, L. Science (1997) [Pubmed]
  4. The DNA helicase activity of yeast Sgs1p is essential for normal lifespan but not for resistance to topoisomerase inhibitors. Mankouri, H.W., Morgan, A. Mech. Ageing Dev. (2001) [Pubmed]
  5. Sgs1: a eukaryotic homolog of E. coli RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation. Watt, P.M., Louis, E.J., Borts, R.H., Hickson, I.D. Cell (1995) [Pubmed]
  6. Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions. Onge, R.P., Mani, R., Oh, J., Proctor, M., Fung, E., Davis, R.W., Nislow, C., Roth, F.P., Giaever, G. Nat. Genet. (2007) [Pubmed]
  7. DNA helicase gene interaction network defined using synthetic lethality analyzed by microarray. Ooi, S.L., Shoemaker, D.D., Boeke, J.D. Nat. Genet. (2003) [Pubmed]
  8. SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination. Myung, K., Datta, A., Chen, C., Kolodner, R.D. Nat. Genet. (2001) [Pubmed]
  9. Association of yeast DNA topoisomerase III and Sgs1 DNA helicase: studies of fusion proteins. Bennett, R.J., Wang, J.C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  10. Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex. Mullen, J.R., Nallaseth, F.S., Lan, Y.Q., Slagle, C.E., Brill, S.J. Mol. Cell. Biol. (2005) [Pubmed]
  11. Distinct roles for the Saccharomyces cerevisiae mismatch repair proteins in heteroduplex rejection, mismatch repair and nonhomologous tail removal. Goldfarb, T., Alani, E. Genetics (2005) [Pubmed]
  12. The hyper unequal sister chromatid recombination in an sgs1 mutant of budding yeast requires MSH2. Onoda, F., Seki, M., Wang, W., Enomoto, T. DNA Repair (Amst.) (2004) [Pubmed]
  13. Characterization of the slow-growth phenotype of S. cerevisiae Whip/Mgs1 Sgs1 double deletion mutants. Branzei, D., Seki, M., Onoda, F., Yagi, H., Kawabe, Y., Enomoto, T. DNA Repair (Amst.) (2002) [Pubmed]
  14. SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Watt, P.M., Hickson, I.D., Borts, R.H., Louis, E.J. Genetics (1996) [Pubmed]
  15. Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae. Onoda, F., Seki, M., Miyajima, A., Enomoto, T. Mol. Gen. Genet. (2001) [Pubmed]
  16. STM1, a gene which encodes a guanine quadruplex binding protein, interacts with CDC13 in Saccharomyces cerevisiae. Hayashi, N., Murakami, S. Mol. Genet. Genomics (2002) [Pubmed]
  17. Functional and physical interaction between Sgs1 and Top3 and Sgs1-independent function of Top3 in DNA recombination repair. Onodera, R., Seki, M., Ui, A., Satoh, Y., Miyajima, A., Onoda, F., Enomoto, T. Genes Genet. Syst. (2002) [Pubmed]
  18. The ability of Sgs1 to interact with DNA topoisomerase III is essential for damage-induced recombination. Ui, A., Seki, M., Ogiwara, H., Onodera, R., Fukushige, S., Onoda, F., Enomoto, T. DNA Repair (Amst.) (2005) [Pubmed]
  19. The N-terminal region of Sgs1, which interacts with Top3, is required for complementation of MMS sensitivity and suppression of hyper-recombination in sgs1 disruptants. Ui, A., Satoh, Y., Onoda, F., Miyajima, A., Seki, M., Enomoto, T. Mol. Genet. Genomics (2001) [Pubmed]
  20. Supercomplex formation between Mlh1-Mlh3 and Sgs1-Top3 heterocomplexes in meiotic yeast cells. Wang, T.F., Kung, W.M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  21. Importance of the Sgs1 helicase activity in DNA repair of Saccharomyces cerevisiae. Saffi, J., Pereira, V.R., Henriques, J.A. Curr. Genet. (2000) [Pubmed]
  22. Binding specificity determines polarity of DNA unwinding by the Sgs1 protein of S. cerevisiae. Bennett, R.J., Keck, J.L., Wang, J.C. J. Mol. Biol. (1999) [Pubmed]
  23. Regulation of homologous integration in yeast by the DNA repair proteins Ku70 and RecQ. Yamana, Y., Maeda, T., Ohba, H., Usui, T., Ogawa, H.I., Kusano, K. Mol. Genet. Genomics (2005) [Pubmed]
  24. Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity. Lo, Y.C., Paffett, K.S., Amit, O., Clikeman, J.A., Sterk, R., Brenneman, M.A., Nickoloff, J.A. Mol. Cell. Biol. (2006) [Pubmed]
  25. Mutations in homologous recombination genes rescue top3 slow growth in Saccharomyces cerevisiae. Shor, E., Gangloff, S., Wagner, M., Weinstein, J., Price, G., Rothstein, R. Genetics (2002) [Pubmed]
  26. Regulation of alternative replication bypass pathways at stalled replication forks and its effects on genome stability: a yeast model. Barbour, L., Xiao, W. Mutat. Res. (2003) [Pubmed]
  27. Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae. Ii, M., Brill, S.J. Curr. Genet. (2005) [Pubmed]
  28. Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae. Kaliraman, V., Brill, S.J. Curr. Genet. (2002) [Pubmed]
  29. Interaction between yeast sgs1 helicase and DNA topoisomerase III. Bennett, R.J., Noirot-Gros, M.F., Wang, J.C. J. Biol. Chem. (2000) [Pubmed]
  30. Trehalose Accumulation in a High-Trehalose-Accumulating Mutant of Saccharomycopsis fibuligera sdu Does Not Respond to Stress Treatments. Liang, L.K., Wang, X.K., Zhu, K.L., Chi, Z.M. Biochemistry Mosc. (2006) [Pubmed]
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