Mitotic checkpoint function in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae.
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.
Myung
Kyungjae
K
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Smith
Stephanie
S
Kolodner
Richard D
RD
D015825:Chromosomes, Fungal / Q000235:genetics*; D004249:DNA Damage; D015321:Gene Rearrangement; D005800:Genes, Fungal; D016681:Genome, Fungal; D042822:Genomic Instability; D008938:Mitosis / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics*