Intermediates of recombination during mating type switching in Saccharomyces cerevisiae.

White, Charles I.; Haber, James E.

doi:10.1002/j.1460-2075.1990.tb08158.x

Cited by 391 publications

(413 citation statements)

References 47 publications

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“…Both strands of the TG 81 ends were well protected in TG-HO and TG-HO-CA cells. Unprotected DSB ends are degraded by 5Ј-to-3Јexonuclease activities, thereby generating 3Ј-ended ssDNA tracts (White and Haber, 1990). Consistently, the 5Ј termini of the TG(Ϫ) ends in HO-CA cells were immediately degraded, whereas the 3Ј termini were protected from DNA degradation.…”

Section: Resultsmentioning

confidence: 82%

“…To facilitate detecting specific signals in hybridization analysis and ChIP assay, we marked the ADH4 locus with the KanMX gene (Wach et al, 1994) ( Figure 1A). DSB ends are degraded by 5Ј-to-3Ј exonuclease activities (White and Haber, 1990), and it is estimated that the 5Ј-to-3Ј degradation occurs at the rate of 4 kb/h (Vaze et al, 2002). Because the ADH4 locus is only 15 kb away from the telomere, we considered the possibility that the completion of the 5Ј-to-3Ј degradation of the 15-kb DNA fragment might attenuate the checkpoint activation.…”

Section: Resultsmentioning

confidence: 99%

“…DNA ends are degraded by 5Ј-to-3Ј exonuclease activities, generating long ssDNA tracts at the 3Ј ends (White and Haber, 1990). In turn, RPA covers the ssDNA region, promoting the recruitment of Mec1 to the DSB ends (Zou and Elledge, 2003).…”

Section: Discussionmentioning

confidence: 99%

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Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Hirano

Sugimoto

2007

MBoC

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Chromosome ends, known as telomeres, have to be distinguished from DNA breaks that activate DNA damage checkpoint. Two large protein kinases, ataxia-teleangiectasia mutated (ATM) and ATM-Rad3-related (ATR), control not only checkpoint activation but also telomere length. In budding yeast, Mec1 and Tel1 correspond to ATR and ATM, respectively. Here, we show that Cdc13-dependent telomere capping attenuates Mec1 association with DNA ends. The telomeric TG repeat sequence inhibits DNA degradation and decreases Mec1 accumulation at the DNA end. The TG-mediated degradation block requires binding of multiple Cdc13 proteins. The Mre11-Rad50-Xrs2 complex and Exo1 contribute to DNA degradation at DNA ends. Although the TG sequence impedes Exo1 association with DNA ends, it allows Mre11 association. Moreover, the TG sequence does not affect Tel1 association with the DNA end. Our results suggest that the Cdc13 telomere cap coordinates Mec1 and Tel1 accumulation rather than simply covering the DNA ends at telomeres. INTRODUCTIONDNA double-strand breaks (DSBs) are induced by exogenous DNA-damaging agents and carcinogens or by endogenous by-products, including reactive oxygen species (Friedberg et al., 2006). The repair of DSBs is crucial for maintaining genome stability. All organisms respond to DSBs by promptly launching the DNA damage response. This response involves the recruitment of DNA repair factors and the activation of signal transduction pathways, often termed DNA damage checkpoint pathways (Zhou and Elledge, 2000). Activation of the checkpoint pathway induces cell cycle arrest and expression of genes required for DNA repair.The checkpoint signals are initiated through two large protein kinases, ataxia-teleangiectasia mutated (ATM) and ATM-Rad3-related (ATR) (Zhou and Elledge, 2000;Abraham, 2001). ATM and ATR are highly conserved among eukaryotes. ATR is closely related to Mec1 in the budding yeast Saccharomyces cerevisiae and Rad3 in the fission yeast Schizosaccharomyces pombe. ATM homologues are termed Tel1 in both budding and fission yeasts. Current evidence indicates that the Mre11-Rad50 -Nbs1 (Xrs2 in budding yeast) complex is the primary sensor that recruits ATR/ Mec1 and ATM/Tel1 to DSBs (Nakada et al., 2003a(Nakada et al., , 2004Falck et al., 2005;You et al., 2005). In budding yeast, there is compelling evidence that the Mre11-Rad50 -Xrs2 (MRX) complex collaborates with exonuclease 1 (Exo1) in the generation of single-stranded DNA (ssDNA) at DSB ends (Krogh and Symington, 2004). ATM/Tel1 interacts with the C terminus of Nbs1/Xrs2 to localize to DNA ends (Nakada et al., 2003a;Falck et al., 2005;You et al., 2005). Meanwhile, the ssDNA that is generated at the DSB is covered with replication protein A (RPA) (Wold, 1997;Krogh and Symington, 2004). RPA-covered DNA recruits ATR/Mec1 to a region near the DSB end (Zou and Elledge, 2003;Nakada et al., 2005). ATM and ATR activate the downstream kinases CHK1 and CHK2 with assistance of checkpoint mediators, including 53BP1, BRCA1, and MDC1 (Zhou and Elledge, 2000;Bakke...

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Section: Resultsmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

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Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Hirano

Sugimoto

2007

MBoC

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“…PCR can be used to identify an intermediate of recombination, the beginnings of new DNA synthesis after strand invasion; this occurs ca. 20-30 min after the DSB can be detected and 30 min before MAT switching is complete (White & Haber 1990). Similar analyses can be done at other loci, by inserting a cloned HO recognition site at another chromosomal location.…”

Section: Introductionmentioning

confidence: 99%

Repairing a double–strand chromosome break by homologous recombination: revisiting Robin Holliday's model

Haber

Ira

Malkova

et al. 2004

Phil. Trans. R. Soc. Lond. B

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Since the pioneering model for homologous recombination proposed by Robin Holliday in 1964, there has been great progress in understanding how recombination occurs at a molecular level. In the budding yeast Saccharomyces cerevisiae, one can follow recombination by physically monitoring DNA after the synchronous induction of a double-strand break (DSB) in both wild-type and mutant cells. A particularly well-studied system has been the switching of yeast mating-type (MAT ) genes, where a DSB can be induced synchronously by expression of the site-specific HO endonuclease. Similar studies can be performed in meiotic cells, where DSBs are created by the Spo11 nuclease. There appear to be at least two competing mechanisms of homologous recombination: a synthesis-dependent strand annealing pathway leading to noncrossovers and a two-end strand invasion mechanism leading to formation and resolution of Holliday junctions (HJs), leading to crossovers. The establishment of a modified replication fork during DSB repair links gene conversion to another important repair process, break-induced replication. Despite recent revelations, almost 40 years after Holliday's model was published, the essential ideas he proposed of strand invasion and heteroduplex DNA formation, the formation and resolution of HJs, and mismatch repair, remain the basis of our thinking.

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“…The DSB ends are subjected to 5Ј to 3Ј directed exonucleolytic processing to leave 3Ј-tailed singlestrand (ss) DNA (Stahl, 1996). These ssDNA tails can be detected in vivo as intermediates during mating-type switching (White and Haber, 1990) and during meiotic recombination (Sun et al, 1989(Sun et al, , 1991Cao et al, 1990). Intermediates with ssDNA tails accumulate if the strand invasion step is blocked by a mutation in the RAD51, gene during mating-type switching and also in DMC1 during meiotic recombination (Bishop et al, 1992;Shinohara et al, 1992;Sugawara and Haber, 1992;Ogawa et al, 1993;Sugawara et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Exo1 Roles for Repair of DNA Double-Strand Breaks and Meiotic Crossing Over inSaccharomyces cerevisiae

Tsubouchi

Ogawa

2000

MBoC

203

188

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The MRE11, RAD50, and XRS2 genes of Saccharomyces cerevisiae are involved in the repair of DNA double-strand breaks (DSBs) produced by ionizing radiation and by radiomimetic chemicals such as methyl methanesulfonate (MMS). In these mutants, single-strand DNA degradation in a 5Ј to 3Ј direction from DSB ends is reduced. Multiple copies of the EXO1 gene, encoding a 5Ј to 3Ј double-strand DNA exonuclease, were found to suppress the high MMS sensitivity of these mutants. The exo1 single mutant shows weak MMS sensitivity. When an exo1 mutation is combined with an mre11 mutation, both repair of MMS-induced damage and processing of DSBs are more severely reduced than in either single mutant, suggesting that Exo1 and Mre11 function independently in DSB processing. During meiosis, transcription of the EXO1 gene is highly induced. In meiotic cells, the exo1 mutation reduces the processing of DSBs and the frequency of crossing over, but not the frequency of gene conversion. These results suggest that Exo1 functions in the processing of DSB ends and in meiotic crossing over.

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Intermediates of recombination during mating type switching in Saccharomyces cerevisiae.

Cited by 391 publications

References 47 publications

Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Repairing a double–strand chromosome break by homologous recombination: revisiting Robin Holliday's model

Exo1 Roles for Repair of DNA Double-Strand Breaks and Meiotic Crossing Over inSaccharomyces cerevisiae

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