Elevation of sister chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom's syndrome gene

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

doi:10.1016/s0921-8777(99)00071-3

Cited by 82 publications

(85 citation statements)

References 33 publications

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“…The same mutation is also listed among the naturally occurring mutations of BLM associated with Bloom's syndrome (Ellis et al, 1995). Moreover, budding yeast cells carrying this mutation in the SGS1 gene show the same DNA-damaging agent sensitivity as that of an sgs1 deletion strain (Onoda et al, 2000).…”

Section: The Core Helicase Domainmentioning

confidence: 85%

RecQ helicases: Multiple structures for multiple functions?

Vindigni

Hickson

2009

HFSP Journal

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Section: The Core Helicase Domainmentioning

confidence: 85%

RecQ helicases: Multiple structures for multiple functions?

Vindigni

Hickson

2009

HFSP Journal

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“…Mutations in either Srs2 or Sgs1 result in a hyperrecombination phenotype (Aguilera and Klein 1988;Onoda et al 2000;Liberi et al 2005). In humans, mutations in BLM, which encodes the human ortholog of Sgs1, give rise to the rare hereditary disorder Bloom's syndrome (Ellis et al 1995).…”

mentioning

confidence: 99%

RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments

Hu¹,

Raynard²,

Sehorn³

et al. 2007

Genes Dev.

289

411

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Members of the RecQ helicase family play critical roles in genome maintenance. There are five RecQ homologs in mammals, and defects in three of these (BLM, WRN, and RECQL4) give rise to cancer predisposition syndromes in humans. RECQL and RECQL5 have not been associated with a human disease. Here we show that deletion of Recql5 in mice results in cancer susceptibility. Recql5-deficient cells exhibit elevated frequencies of spontaneous DNA double-strand breaks and homologous recombination (HR) as scored using a reporter that harbors a direct repeat, and are prone to gross chromosomal rearrangements in response to replication stress. To understand how RECQL5 regulates HR, we use purified proteins to demonstrate that human RECQL5 binds the Rad51 recombinase and inhibits Rad51-mediated D-loop formation. By biochemical means and electron microscopy, we show that RECQL5 displaces Rad51 from single-stranded DNA (ssDNA) in a reaction that requires ATP hydrolysis and RPA. Together, our results identify RECQL5 as an important tumor suppressor that may act by preventing inappropriate HR events via Rad51 presynaptic filament disruption.[Keywords: Recql5 helicase; DNA repair; homologous recombination; tumor suppressor; Rad51 recombinase] Supplemental material is available at http://www.genesdev.org.

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“…RecQ mutants show increased rates of HR (21-25). BS patients show very high levels of sister-chromatid exchanges, whereas, in yeast cells, sgs1 and rqh1 mutants have increased levels of HR, based on studies using various reporter systems (17,(26)(27)(28). HR is responsible for the synthetic lethality seen between sgs1͞rqh1 and srs2, another DNA helicase gene (29,30).…”

mentioning

confidence: 99%

Rqh1 blocks recombination between sister chromatids during double strand break repair, independent of its helicase activity

Hope

Mense

Jalakas

et al. 2006

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

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Many questions remain about the process of DNA double strand break (DSB) repair by homologous recombination (HR), particularly concerning the exact function played by individual proteins and the details of specific steps in this process. Some recent studies have shown that RecQ DNA helicases have a function in HR. We studied the role of the RecQ helicase Rqh1 with HR proteins in the repair of a DSB created at a unique site within the Schizosaccharomyces pombe genome. We found that DSBs in rqh1 ؉ cells, are predominantly repaired by interchromosomal gene conversion, with HR between sister chromatids [sister-chromatid conversion (SCC)], occurring less frequently. In ⌬rqh1 cells, repair by SCC is favored, and gene conversion rates slow significantly. When we limited the potential for SCC in ⌬rqh1 cells by reducing the length of the G2 phase of the cell cycle, DSB repair continued to be predominated by SCC, whereas it was essentially eliminated in wild-type cells. These data indicate that Rqh1 acts to regulate DSB repair by blocking SCC. Interestingly, we found that this role for Rqh1 is independent of its helicase activity. In the course of these studies, we also found nonhomologous end joining to be largely faithful in S. pombe, contrary to current belief. These findings provide insight into the regulation of DSB repair by RecQ helicases.homologous recombination ͉ nonhomologous end joining ͉ rqh1 ͉ gene conversion D ouble strand breaks (DSBs) pose a major problem for genomic instability and cell survival, because a single unrepaired DSB is, presumably, sufficient to cause cell death (1). The sources of DSBs can be either endogenous, such as those induced during the reshuffling of DNA in Ig gene diversification, or exogenous, such as those induced by exposure to ionizing radiation (2-4). The cell has two major mechanisms for the repair of DSBs: homologous recombination (HR) and nonhomologous end joining (NHEJ), each used to varying degrees in different organisms (2,3,5,6). HR is characterized as an error-free process using homologous sequences as the template to repair the DSB. Repair by HR begins with the formation of 3Ј single strand ends at the break that can then invade homologous duplex DNA. The 3Ј end of the invading strand is extended by DNA polymerase. At this point, the DSB can be repaired by either DSB repair, which involves formation of a double Holliday junction (HJ) or synthesis-dependent strand annealing (3, 7).In NHEJ, the DNA ends are resealed by rejoining the broken ends; however, this process can lead to loss of information at the break and is, thus, referred to as error-prone repair (5,8). Whereas mammalian cells preferentially use NHEJ over HR, budding yeast, for the most part, use HR over NHEJ. In Saccharomyces cerevisiae, the MRX (MRN in Schizosaccharomyces pombe) complex has been shown to play a role in NHEJ (9, 10). In S. pombe, only pKu70͞80 and Ligase IV have been identified as functioning in NHEJ, and MRN does not appear to be active in this process (11).RecQ DNA helicases are found in vi...

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Elevation of sister chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom's syndrome gene

Cited by 82 publications

References 33 publications

RecQ helicases: Multiple structures for multiple functions?

RecQ helicases: Multiple structures for multiple functions?

RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments

Rqh1 blocks recombination between sister chromatids during double strand break repair, independent of its helicase activity

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