The<i>Saccharomyces cerevisiae</i>checkpoint genes RAD9, CHK1 and PDS1 are required for elevated homologous recombination in a mec1 (ATR) hypomorphic mutant

Fasullo, Michael; Sun, Mingzeng

doi:10.4161/cc.6411

Cited by 12 publications

(20 citation statements)

References 35 publications

(58 reference statements)

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“…We previously observed a 6-fold increase in the rate of spontaneous SCE in the mec1-21 mutant (YB312) compared to wild-type (18). We observed no difference in the rates of spontaneous recombination between sml1 (YB326) and wild-type (YB163); however the 6-fold increase in rates of SCE was reduced to wild-type levels in mec1-21 sml1 (YB329, Table 2).…”

Section: Resultsmentioning

confidence: 96%

“…ADE2 results from heteroallelic recombination between ade2-a and ade2-n generates; red sectors are Ade − and white sectors are Ade + (18). Colony phenotypes are shown for MEC1 (wild-type, YB348), sml1 (YB323), mec1-21 (YB325) and mec1-21 sml1 (YB375).…”

Section: Resultsmentioning

confidence: 99%

“…RAD52 is required for double-strand break repair (for review, 16), and compared to mec1-21, viability in the mec1-21 rad52 mutant is significantly reduced, suggesting that double-strand breaks spontaneously arise in mec1-21 (17). Our previous studies have indicated that compared to wild-type, mec1-21 exhibits significantly higher rates of spontaneous homologous recombination between sister chromatids, homologs and non-homologous chromosomes (18). The hyper-recombination phenotype is dependent on RAD52 and G2 checkpoint genes (18), suggesting that spontaneous DNA breaks generated by DNA replication are repaired by homologous recombination.…”

Section: Introductionmentioning

confidence: 99%

“…Our previous studies have indicated that compared to wild-type, mec1-21 exhibits significantly higher rates of spontaneous homologous recombination between sister chromatids, homologs and non-homologous chromosomes (18). The hyper-recombination phenotype is dependent on RAD52 and G2 checkpoint genes (18), suggesting that spontaneous DNA breaks generated by DNA replication are repaired by homologous recombination.…”

Section: Introductionmentioning

confidence: 99%

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Elevated dNTP levels suppress hyper-recombination in Saccharomyces cerevisiae S-phase checkpoint mutants

Fasullo

Tsaponina

Sun

et al. 2009

Nucleic Acids Research

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MEC1, the essential yeast homolog of the human ATR/ATM genes, controls the S-phase checkpoint and prevents replication fork collapse at slow zones of DNA replication. The viability of hypomorphic mec1-21 is reduced in the rad52 mutant, defective in homologous recombination, suggesting that replication generates recombinogenic lesions. We previously observed a 6-, 10- and 30-fold higher rate of spontaneous sister chromatid exchange (SCE), heteroallelic recombination and translocations, respectively, in mec1-21 mutants compared to wild-type. Here we report that the hyper-recombination phenotype correlates with lower deoxyribonucleoside triphosphate (dNTP) levels, compared to wild-type. By introducing a dun1 mutation, thus eliminating inducible expression of ribonucleotide reductase in mec1-21, rates of spontaneous SCE increased 15-fold above wild-type. All the hyper-recombination phenotypes were reduced by SML1 deletions, which increase dNTP levels. Measurements of dNTP pools indicated that, compared to wild-type, there was a significant decrease in dNTP levels in mec1-21, dun1 and mec1-21 dun1, while the dNTP levels of mec1-21 sml1, mec1-21 dun1 sml1 and sml1 mutants were ∼2-fold higher. Interestingly, higher dNTP levels in mec1-21 dun1 sml1 correlate with ∼2-fold higher rate of spontaneous mutagenesis, compared to mec1-21 dun1. We suggest that higher dNTP levels in specific checkpoint mutants suppress the formation of recombinogenic lesions.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elevated dNTP levels suppress hyper-recombination in Saccharomyces cerevisiae S-phase checkpoint mutants

Fasullo

Tsaponina

Sun

et al. 2009

Nucleic Acids Research

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“…There is growing evidence that signaling pathways regulating the DDR intersect with the mitotic spindle checkpoint pathways. In budding yeast, Pds1 is a central protein essential for both the spindle checkpoint and the DNA damage checkpoint [16]. In mammalian cells, a number of DNA damage responsive elements, including Chk1, Chk2, Brca1-Bard1 and Brca2, have been reported to play a role in spindle checkpoint activation [17-21].…”

Section: Discussionmentioning

confidence: 99%

The kinetochore protein Bub1 participates in the DNA damage response

Yang

Wang

et al. 2012

DNA Repair

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The DNA damage response (DDR) and the spindle assembly checkpoint (SAC) are two critical mechanisms by which mammalian cells maintain genome stability. There is a growing body of evidence that DDR elements and SAC components crosstalk. Here we report that Bub1 (Budding Uninhibited by Benzimidazoles 1), one of the critical kinetochore proteins essential for SAC, is required for optimal DDRs. We found that knocking-down Bub1 resulted in prolonged H2AX foci and comet tail formation as well as hypersensitivity in response to ionizing radiation (IR). Further, we found that Bub1-mediated Histone H2A Threonine 121 phosphorylation was induced after IR in an ATM-dependent manner. We demonstrated that ATM phosphorylated Bub1 on serine 314 in response to DNA damage in vivo. Finally, we showed that ATM-mediated Bub1 serine 314 phosphorylation was required for IR-induced Bub1 activation and for the optimal DDR. Together, we elucidate the molecular mechanism of DNA damage-induced Bub1 activation and highlight a critical role of Bub1 in DDR.

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Current awareness on yeast

2009

Yeast

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In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Reviews; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (8 weeks journals ‐ search completed 31st. Dec. 2008)

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TheSaccharomyces cerevisiaecheckpoint genes RAD9, CHK1 and PDS1 are required for elevated homologous recombination in a mec1 (ATR) hypomorphic mutant

Cited by 12 publications

References 35 publications

Elevated dNTP levels suppress hyper-recombination in Saccharomyces cerevisiae S-phase checkpoint mutants

Elevated dNTP levels suppress hyper-recombination in Saccharomyces cerevisiae S-phase checkpoint mutants

The kinetochore protein Bub1 participates in the DNA damage response

Current awareness on yeast

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