Induction of mating type interconversion in a heterothallic strain of Saccharomyces cerevisiae by DNA damaging agents

Mating type interconversion of the yeast, Saccharomyces cerevisiae, is an example of a directed genome rearrangement leading to a change in gene expression and in the differentiation state of a cell. In heterothallic haploid cells this switching of the mating type from a to alpha or vice versa, which is accomplished by an intrachromosomal gene conversion mechanism, is a rare event, happening about once per 10(6) cells per generation. Those cells that have changed their mating type can be trapped as diploid colonies by making them mate with tester cells possessing complementary markers. We found that treating haploids with UV light or with chemical carcinogens before they could mate resulted in a significant and dose-dependent enhancement of the numbers of diploid colonies. By genetic as well as by DNA hybridization analyses, these diploid clones were proved to be descendants of haploids which had changed their mating type by the bona fide gene conversion process. Thus, the DNA damaging agents had caused the induction of a directed gene rearrangement. It is suggested that induction of genome rearrangements might be part of a general response to DNA damage, at least in yeast cells. If similar responses also took place in cell populations constituting multicellular organisms, induced gene rearrangements and a generally enhanced mobility of the genome as a consequence of DNA damage might play a determining role in chemical and radiation-induced carcinogenesis.