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In the present study, low doses of methyl methane sulfonate that activate the intra-S checkpoint but not the G\n            <jats:sub>1<\/jats:sub>\n            or G\n            <jats:sub>2<\/jats:sub>\n            DNA damage checkpoints were found to cause increased accumulation of genome rearrangements in both wild-type strains and to an even greater extent in strains containing mutations causing defects in the intra-S checkpoint. The rearrangements were primarily translocations or events resulting in deletion of a portion of a chromosome arm along with the addition of a new telomere. Combinations of mutations causing individual defects in the RAD24 or SGS1 branches of the intra-S checkpoint or the replication checkpoint showed synergistic interactions with regard to the spontaneous genome instability rate. PDS1 and the RAD50\u2013MRE11\u2013XRS2 complex were found to be important members of all the S-phase checkpoints in suppressing genome instability, whereas RAD53 only seemed to play a role in the intra-S checkpoints. Combinations of mutations that seem to result in inactivation of the S-phase checkpoints and critical effectors resulted in as much as 12,000\u201314,000-fold increases in the genome instability rate. These data support the view that spontaneous genome rearrangements result from DNA replication errors and indicate that there is a high degree of redundancy among the checkpoints that act in S phase to suppress such genome instability.\n          <\/jats:p>","DOI":"10.1073\/pnas.062702199","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:37:36Z","timestamp":1027694256000},"page":"4500-4507","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":113,"title":["Suppression of genome instability by redundant S-phase checkpoint pathways in\n            <i>Saccharomyces<\/i>\n            <i>cerevisiae<\/i>"],"prefix":"10.1073","volume":"99","author":[{"given":"Kyungjae","family":"Myung","sequence":"first","affiliation":[{"name":"Ludwig Institute for Cancer Research, Cancer Center, and Department of Medicine, University of California at San Diego School of Medicine, La Jolla, CA 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