Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae

Onoda, Fumitoshi; Seki, Masayuki; Miyajima, Atsuko; Enomoto, Takemi

doi:10.1007/s004380000358

Cited by 57 publications

(44 citation statements)

References 19 publications

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“…The two models arise because the situation is more complex for Sgs1. The sgs1 mutation decreases the rates of conversion induced by genotoxic agents as compared with the wild-type responses (16,49) but increases that of untreated cells (37). Thus, Sgs1 plays both positive and negative roles in recombination, which may or may not be related to its role in the intra-S-phase checkpoint (19,50).…”

Section: Are Mus81͞mms4 Sgs1͞top3 and Srs2 Involved In Replication Ormentioning

confidence: 99%

Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication

Fabre

Chan

Heyer

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

298

360

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Toxic recombination events are detected in vegetative Saccharomyces cerevisiae cells through negative growth interactions between certain combinations of mutations. For example, mutations affecting both the Srs2 and Sgs1 helicases result in extremely poor growth, a phenotype suppressed by mutations in genes that govern early stages of recombination. Here, we identify a similar interaction involving double mutations affecting Sgs1 or Top3 and Mus81 or Mms4. We also find that the primary DNA structures that initiate these toxic recombination events cannot be double-strand breaks and thus are likely to be single-stranded DNA. We interpret our results in the context of the idea that replication stalling leaves single-stranded DNA, which can then be processed by two competing mechanisms: recombination and nonrecombination gap-filling. Functions involved in preventing toxic recombination would either avoid replicative defects or act on recombination intermediates. Our results suggest that Srs2 channels recombination intermediates back into the gap-filling route, whereas Sgs1/Top3 and Mus81/Mms4 are involved in recombination and/or in replication to allow replication restart

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Section: Are Mus81͞mms4 Sgs1͞top3 and Srs2 Involved In Replication Ormentioning

confidence: 99%

Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication

Fabre

Chan

Heyer

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

298

360

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“…A role for MUS81-MMS4 in recombination was implied from its functional overlap with SGS1-TOP3 ). In the yeasts, there is good evidence that the RecQ-Top3 complex functions in the HR pathway (Wu et al 1998(Wu et al , 2001Gangloff et al 1999;Onoda et al 2001;Maftahi et al 2002;Oakley et al 2002;Shor et al 2002;Laursen et al 2003;Hope et al 2005). The notion that MUS81 might act downstream of RAD51 was further suggested by the suppression of mus81 sgs1 synthetic-lethality by rad51 (Fabre et al 2002;Bastin-Shanower et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…In the yeast Saccharomyces cerevisiae, loss of the SGS1 DNA helicase results in genome instability, including increased rates of mitotic and meiotic recombination, gross chromosomal rearrangements, and chromosome loss (Watt et al 1995(Watt et al , 1996Sinclair et al 1997;Yamagata et al 1998;Chakraverty and Hickson 1999;Myung et al 2001;Onoda et al 2001;Hickson 2003). In addition, sgs1 mutants are sensitive to high levels of DNA-damaging agents such as ultraviolet light (UV), methylmethane sulfonate (MMS) and hydroxyurea (HU) (Yamagata et al 1998;Mullen et al 2000) presumably because of their effects on DNA replication.…”

Section: Introductionmentioning

confidence: 99%

Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae

Miki¹,

Brill²

2005

Curr Genet

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Yeast cells lacking the SGS1 DNA helicase and the MUS81 structure-specific endonuclease display a synthetic lethality that is suppressed by loss of the RAD51 recombinase. This epistatic interaction suggests that the primary function of SGS1 or MUS81, or both genes, is downstream of RAD51. To identify RAD51-independent functions of SGS1 and MUS81, a synthetic-lethal screen was performed on the sgs1 mus81 rad51 triple mutant. We found that mutation of RNH202, which encodes a subunit of the hetero-trimeric RNase H2, generates a profound synthetic-sickness in this background. RNase H2 is thought to play a non-essential role in Okazaki fragment maturation. Cells lacking RNH202 showed synthetic growth defects when combined with either mus81 or sgs1 alone. But, whereas the loss of RAD51 had little effect on rnh202 sgs1 double mutants, it strongly inhibited the growth of rnh202 mus81 cells. These data indicate that the primary function of SGS1, but not MUS81, is downstream of RAD51. SGS1 must have some RAD51-independent function, however, since the growth of rnh202 mus8 1rad51 cells was further compromised by the loss of SGS1. Consistent with these results, we show that rnh202 cells display a sensitivity to DNA-damaging agents that is exacerbated in the absence of RAD51 or MUS81. These data support a model in which defects in lagging-strand replication are repaired by the Mus81 endonuclease or through a pathway dependent on Rad51 and Sgs1.

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“…Like the yeast sgs1 disruptants that show an increased frequency of spontaneous recombination (Watt et al, 1996;Onoda et al, 2001), BLM 7/7 DT40 cells have a hyper-recombination phenotype resulting in increased frequencies in both SCEs and targeted genome integration (Imamura et al, 2001). Sonoda et al (1999) demonstrated that HR between sister chromatids is the primary mechanism for SCE in DT40 cells.…”

Section: Possible Involvement Of Wrn In Homologous Recombinationmentioning

confidence: 99%

Werner and Bloom helicases are involved in DNA repair in a complementary fashion

et al. 2002

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Werner syndrome (WS) is a recessive disorder characterized by premature senescence. Bloom syndrome (BS) is a recessive disorder characterized by short stature and immunode®ciency. A common characteristic of both syndromes is genomic instability leading to tumorigenesis. WRN and BLM genes causing WS and BS, encode proteins that are closely related to the RecQ helicase. We produced WRN 7/7, BLM 7/7 and WRNmutants in the chicken B-cell line DT40. WRN 7/7 cells showed hypersensitivities to genotoxic agents, such as 4-nitroquinoline 1-oxide, camptothecin and methyl methanesulfonate. They also showed a threefold increase in targeted integration rate of exogenous DNAs, but not in sister chromatid exchange (SCE) frequency. BLM 7/7 cells showed hypersensitivities to the genotoxic agents as well as ultraviolet (UV) light, in addition to a 10-fold increase in targeted integration rate and an 11-fold increase in SCE frequency. In WRN 7/7 /BLM 7/7 cells, synergistically increased hypersensitivities to the genotoxic agents were observed whereas both SCE frequencies and targeted integration rates were partially diminished compared to the single mutants. Chromosomal aberrations were also synergistically increased in WRN 7/7 / BLM 7/7 cells when irradiated with UV light in late S to G 2 phases. These results suggest that both WRN and BLM may be involved in DNA repair in a complementary fashion.

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Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae

Cited by 57 publications

References 19 publications

Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication

Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication

Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae

Werner and Bloom helicases are involved in DNA repair in a complementary fashion

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