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

Abstract

Cancer cells show increased genome rearrangements, although it is unclear what defects cause these rearrangements. Mutations in Saccharomyces cerevisiae RFC5, DPB11, MEC1, DDC2 MEC3, RAD53, CHK1, PDS1, and DUN1 increased the rate of genome rearrangements up to 200-fold whereas mutations in RAD9, RAD17, RAD24, BUB3, and MAD3 had little effect. The rearrangements were primarily deletion of a portion of a chromosome arm along with TEL1-dependent addition of a new telomere. tel1 mutations increased the proportion of translocations observed, and in some cases showed synergistic interactions when combined with mutations that increased the genome rearrangement rate. These data suggest that one role of S phase checkpoint functions in normal cells is to suppress spontaneous genome rearrangements resulting from DNA replication errors.