To determine the effect of aneuploidy on genomic stability, Sheltzer et al. analysed 13 haploid Saccharomyces cerevisiae strains that each carried an additional copy of a different chromosome. These aneuploid strains were known to have proliferative defects compared with wild-type strains, but the authors found that most aneuploid strains are also impaired in the faithful segregation of chromosomes into daughter cells. However, the genomic instability in these aneuploid cells was not only at the level of whole chromosomes. The mutation rate of specific genes (URA3 and CAN1) was increased in some aneuploid lines.
What causes the increased mutation rate of these aneuploid cells? The authors found that they have increased sensitivity to multiple DNA-damaging agents and also that both the resulting DNA damage and Rad52-containing DNA repair foci persist in cells. These features indicate that a defect in homologous recombination-based DNA repair might contribute to the increased rate of mutation. Indeed, DNA sequencing revealed that the focal mutations are likely to be caused by the error-prone DNA polymerase Pol ζ, which is used in a back-up repair mechanism in the absence of homologous recombination.
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