Lack of DNA homology in a pair of divergent chromosomes greatly sensitizes them to loss by DNA damage

Abstract

Chromosomal DNA is considered a priori to be a target for the induction of numerical (whole chromosome) aneuploidy in mitotic cells. If true, DNA repair would be expected to contribute to genome stability. One type of repair that appears to play an important role in the response of many organisms to DNA-damaging agents involves recombination. Using the yeast Saccharomyces cerevisiae containing a pair of DNA divergent (homoeologous) chromosomes, we have been able to determine the importance of recombinational repair of DNA damage in the maintenance of chromosome number. Specifically, the induction of aneuploidy by ionizing radiation has been examined in diploids that had one chromosome III replaced by a divergent chromosome from Saccharomyces carlsbergensis. The chromosomes are functionally equivalent but lack precise DNA homology over one-half their length. The absence of homology, and thus the opportunity for recombinational repair (presumably of DNA double-strand breaks) in the divergent chromosomes, results in high levels (5-10%) of aneuploidy for chromosome III at doses of radiation resulting in almost no killing. For homologous chromosomes, the frequency of loss is 20-50 times lower.