Sgs1: A eukaryotic homolog of E. coil RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation

Watt, Paul M.; Louis, Edward J.; Borts, Rhona H.; Hickson, Ian D.

doi:10.1016/0092-8674(95)90335-6

Cited by 390 publications

(340 citation statements)

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“…Functional interaction between proteins involved in DNA replication, such as replication protein A (RPA) and DNA polymerase ␦, and WRN also have been reported (Shen et al, 1998;Brosh et al, 1999;Kamath-Loeb et al, 2000). Furthermore, in yeast, the RecQlike proteins seem involved in suppression of hyperrecombination, S-phase checkpoint control, and correct DNA segregation (Gangloff et al, 1994, Watt et al, 1995Stewart et al, 1997;Davey et al, 1998;Yamagata et al, 1998;Frei and Gasser, 2000). Noteworthy, yeast mutants in such RecQ-like helicases are extremely sensitive to agents that cause replication arrest, such as hydroxyurea because of uncontrolled illegitimate recombinational events (Stewart et al, 1997;Yamagata et al, 1998).…”

Section: Introductionmentioning

confidence: 98%

Werner's Syndrome Protein Is Required for Correct Recovery after Replication Arrest and DNA Damage Induced in S-Phase of Cell Cycle

Pichierri

Franchitto

Mosesso

et al. 2001

MBoC

138

140

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Werner's syndrome (WS) is a rare autosomal recessive disorder that arises as a consequence of mutations in a gene coding for a protein that is a member of RecQ family of DNA helicases, WRN. The cellular function of WRN is still unclear, but on the basis of the cellular phenotypes of WS and of RecQ yeast mutants, its possible role in controlling recombination and/or in maintenance of genomic integrity during S-phase has been envisaged. With the use of two drugs, camptothecin and hydroxyurea, which produce replication-associated DNA damage and/or inhibit replication fork progression, we find that WS cells have a slower rate of repair associated with DNA damage induced in the S-phase and a reduced induction of RAD51 foci. As a consequence, WS cells undergo apoptotic cell death more than normal cells, even if they arrest and resume DNA synthesis at an apparently normal rate. Furthermore, we report that WS cells show a higher background level of DNA strand breaks and an elevated spontaneous induction of RAD51 foci. Our findings support the hypothesis that WRN could be involved in the correct resolution of recombinational intermediates that arise from replication arrest due to either DNA damage or replication fork collapse. INTRODUCTIONWerner's syndrome (WS) is a rare autosomal recessive disorder characterized by premature aging (Salk et al., 1985) and early onset of various neoplasms, including different types of carcinomas and sarcomas (Goto et al., 1981;Hrabko et al., 1982;Sato et al., 1988). This disorder arises as a consequence of mutations in a gene coding for a protein that is a member of RecQ family of DNA helicases, WRN. One of the hallmarks of WS patients is the genomic instability as evidenced by the spontaneous chromosome anomalies and large deletions in many genes (Salk et al., 1985;Fukuchi et al., 1989). It has been demonstrated that WRN exhibits DNA unwinding activity (Gray et al., 1997;Suzuki et al., 1997) and exonuclease activity residing in the N-terminal region (Huang et al., 1998). The cellular function of WRN is still unclear. It has been proposed that helicases are required for various DNA metabolic activities, including progression of replication fork, segregation of newly replicated chromosomes, disruption of the nucleosome structure, DNA supercoiling, transcription, recombination, and repair (Duguet, 1997). In addition, it has been suggested that RecQ family of DNA helicases has an important role in the maintenance of genomic integrity during DNA replication . Studies from yeast show that DNA replication does not proceed normally in absence of RecQ helicase function (Stewart et al., 1997) and in Xenopus laevis the ortholog of WRN is absolutely required for proper formation of replication foci (Yan et al., 1998). Functional interaction between proteins involved in DNA replication, such as replication protein A (RPA) and DNA polymerase ␦, and WRN also have been reported (Shen et al., 1998;Brosh et al., 1999;Kamath-Loeb et al., 2000). Furthermore, in yeast, the RecQlike proteins seem involved in ...

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Section: Introductionmentioning

confidence: 98%

Werner's Syndrome Protein Is Required for Correct Recovery after Replication Arrest and DNA Damage Induced in S-Phase of Cell Cycle

Pichierri

Franchitto

Mosesso

et al. 2001

MBoC

138

140

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“…In budding yeast, a single RecQ member is encoded by the SGS1 gene. It is a 3 -5 DNA helicase (Bennett et al, 1998) interacting with topoisomerases Top3 and Top2 (Gangloff et al, 1994;Watt et al, 1995). Another ATP-dependent DNA helicase with 3 -5 polarity, playing a role in genome stability, is encoded by the MPH1 gene from Saccharomyces cerevisiae (Scheller et al, 2000;Prakash et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Panico

Ede

Schildmann

et al. 2009

Yeast

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In yeast as in human, DNA helicases play critical roles in assisting replication fork progression. The Saccharomyces cerevisiae MPH1 gene, homologue of human FANCM, has been involved in homologous recombination and DNA repair. We describe a synthetic growth defect of an mph1 deletion if combined with an srs2 deletion that can result -depending on the genetic background -in synthetic lethality. The lethality is suppressed by mutations in homologous recombination (rad51, rad52, rad55, rad57 ) and in the DNA damage checkpoint (rad9, rad24, rad17 ). Importantly, rad54 and mph1, epistatic for damage sensitivity, are subadditive for spontaneous mutator phenotype. Therefore, Mph1 could be placed at the Rad51-mediated strand invasion process, with a function distinct from Rad54. Moreover, siz1 mutation is viable with mph1 and additive for DNA damage sensitivity. mph1 srs2 double mutants, isolated in a background where they are viable, are synergistically sensitive to DNA damage. Moderate overexpression of SGS1 partially suppresses this sensitivity. Finally, we observe an epistatic relationship in terms of sensitivity to camptothecin of mms4 or mus81 to mph1. Overall, our results support a role of Mph1 in assisting replication progression. We propose two models for the resumption of DNA synthesis under replicative stress where Mph1 is placed at the sister chromatid interaction step.

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“…The BLM protein has been identi®ed as a member in the DExH boxcontaining RecQ helicase subfamily (Ellis et al, 1995). Its primary sequence presents similarities with all known members in the RecQ subfamily, including Escherichia coli RecQ (Umezu et al, 1990), Saccharomyces cerevisiae Sgs1p (Ganglo et al, 1994;Watt et al, 1995), Schizosaccharomyces pombe Rqh1 (Stewart et al, 1997), Drosophila melanogaster DmBLM (Kusano et al, 1999), human RecQL (Puranam and Blackshear, 1994;Seki et al, 1994), human Wrn, the product of the Werner's syndrome gene (Yu et al, 1996) and the recently identi®ed human RecQ4 and RecQ5 proteins (Kitao et al, 1998). Chester et al (1998) developed a mouse model for the human Bloom's syndrome, and showed that mouse embryos homozygous for a targeted mutation in the murine Bloom's syndrome gene die by embryonic day 13.5, but little is known about function(s) of BLM.…”

Section: Introductionmentioning

confidence: 99%

Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase

et al. 2000

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Bloom's syndrome (BS) is a rare human autosomal recessive disorder characterized by an increased risk to develop cancer of all types. BS cells are characterized by a generalized genetic instability including a high level of sister chromatid exchanges. BS arises through mutations in both alleles of the BLM gene which encodes a 3' ± 5' DNA helicase identi®ed as a member of the RecQ family. We developed polyclonal antibodies speci®c for the NH 2 -and COOH-terminal region of BLM. Using these antibodies, we analysed BLM expression during the cell cycle and showed that the BLM protein accumulates to high levels in S phase, persists in G2/ M and sharply declines in G1, strongly suggestive of degradation during mitosis. The BLM protein is subject to post-translational modi®cations in mitosis, as revealed by slow migrating forms of BLM found in both demecolcine-treated cells and in mitotic cells isolated from non-treated asynchronous populations. Phosphatase treatment indicated that phosphorylation events were solely responsible for the appearance of the retarded moieties, a possible signal for subsequent degradation. Together, these results are consistent with a role of BLM in a replicative (S phase) and/or post-replicative (G2 phase) process.

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Sgs1: A eukaryotic homolog of E. coil RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation

Cited by 390 publications

References 31 publications

Werner's Syndrome Protein Is Required for Correct Recovery after Replication Arrest and DNA Damage Induced in S-Phase of Cell Cycle

Werner's Syndrome Protein Is Required for Correct Recovery after Replication Arrest and DNA Damage Induced in S-Phase of Cell Cycle

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase

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