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

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.

Fig. 1.

Enhanced sensitivity to temperature and DNA-damaging agents caused by defects in the mitotic checkpoint and the MEN. Strains with the indicated genotypes were tested for sensitivity to temperature, MMS, or UV irradiation as described in Materials and Methods. Each row from left to right shows 1:10 serial dilutions.

Fig. 2.

Model for the relationship between the mitotic checkpoint and MEN genes and the formation of GCRs. (A) Models illustrate genetic interactions among checkpoint genes. P, phosphorylation. (B) Model for the interaction between checkpoint activation and either the formation of GCRs or lethality.