Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae

Cancer cells show increased genome rearrangements, although it is unclear w hat defects cause these rearrangements. Mutations in Saccharomyces cerevisi ae RFC5, DPB11, MEC1, DDC2 MEC3, RAD53, CHK1, PDS1, and DUN1 increased the rate of genome rearrangements up to 200-fold whereas mutations in RAD9, RAD 17, RAD24, BUB3, and MAD3 had little effect. The rearrangements were primar ily deletion of a portion of a chromosome arm along with TEL1-dependent add ition of a new telomere. tell mutations increased the proportion of translo cations observed, and in some cases showed synergistic interactions when co mbined with mutations that increased the genome rearrangement rate. These d ata suggest that one role of S phase checkpoint functions in normal cells i s to suppress spontaneous genome rearrangements resulting from DNA replicat ion errors.