A Fine-Structure Map of Spontaneous Mitotic Crossovers in the Yeast Saccharomyces cerevisiae

Abstract

Homologous recombination is an important mechanism for the repair of DNA damage in mitotically dividing cells. Mitotic crossovers between homologues with heterozygous alleles can produce two homozygous daughter cells (loss of heterozygosity), whereas crossovers between repeated genes on non-homologous chromosomes can result in translocations. Using a genetic system that allows selection of daughter cells that contain the reciprocal products of mitotic crossing over, we mapped crossovers and gene conversion events at a resolution of about 4 kb in a 120-kb region of chromosome V of Saccharomyces cerevisiae. The gene conversion tracts associated with mitotic crossovers are much longer (averaging about 12 kb) than the conversion tracts associated with meiotic recombination and are non-randomly distributed along the chromosome. In addition, about 40% of the conversion events have patterns of marker segregation that are most simply explained as reflecting the repair of a chromosome that was broken in G1 of the cell cycle. Most higher organisms have two copies of several different types of chromosomes. For example, the human female has 23 pairs of chromosomes. Although the chromosome pairs have very similar sequences, they are not identical. Members of a chromosome pair can swap segments from one chromosome to the other; these exchanges are called “recombination.” Most previous studies of recombination have been done in cells undergoing meiosis, the process that leads to the formation of eggs and sperm (gametes). Recombination, however, can also occur in cells that are dividing mitotically. In our study, we examine the properties of mitotic recombination in yeast. We show that mitotic recombination differs from meiotic recombination in two important ways. First, the sizes of the chromosome segments that are non-reciprocally transferred during mitotic recombination are much larger than those transferred during meiotic exchange. Second, in meiosis, most recombination events involve the repair of a single chromosome break, whereas in mitosis, about half of the recombination events appear to involve the repair of two chromosome breaks.