Mitotic checkpoint function in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae

doi:10.1073/pnas.0407010101

Mitotic checkpoint function in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae

^*National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; and ^†Ludwig Institute for Cancer Research, University of California at San Diego School of Medicine, La Jolla, CA 92093

Contributed by Richard D. Kolodner, September 23, 2004

Abstract

The accumulation of gross chromosomal rearrangements (GCRs) is characteristic of cancer cells. Multiple pathways that prevent GCRs, including S-phase cell cycle checkpoints, homologous recombination, telomere maintenance, suppression of de novo telomere addition, chromatin assembly, and mismatch repair, have been identified in Saccharomyces cerevisiae. However, pathways that promote the formation of GCRs are not as well understood. Of these, the de novo telomere addition pathway and nonhomologous end-joining are the best characterized. Here, we demonstrate that defects in the mitotic checkpoint and the mitotic exit network can suppress GCRs in strains containing defects that increase the GCR rate. These data suggest that functional mitotic checkpoints can play a role in the formation of genome rearrangements.

Footnotes

↵ ‡ To whom correspondence should be addressed at: Ludwig Institute for Cancer Research, University of California at San Diego School of Medicine, CMME3058, 9500 Gilman Drive, La Jolla, CA 92093-0669. E-mail: rkolodner{at}ucsd.edu.
Abbreviations: Can^r, canavanine-resistant; 5-FOA^r, 5-fluoroorotic acid-resistant; GCR, gross chromosomal rearrangement; MEN, mitotic exit network; MMS, methyl methanesulfonate.