Mitotic Recombination: Why? When? How? Where?

Abstract

DNA damage repair, loss of heterozygosity, and chromosome rearrangement are important aspects of genome stability, and all are tied to mitotic recombination. Despite the importance of mitotic recombination, the most basic questions about this process remain poorly understood. This is in part because mitotic recombination, in contrast to meiotic recombination, is rare on a per cell division basis [1]. A number of systems have been devised to detect or select for mitotic recombination. In this issue of PLoS Genetics, Lee et al. [2] describe a novel system that represents a major step forward in the study of spontaneous mitotic recombination events. Their studies have given us new insights into the why, when, how, and where of mitotic recombination. Mitotic recombination was first described by Stern in his classic Drosophila experiments [3]. For Stern, “recombination” referred only to reciprocal crossovers (RCOs) (Figure 1A). A severe limitation of most RCO assays is that only one of the two reciprocal products can be recovered. Barbera and Petes [4] devised a clever method to recover both products of RCOs in Saccharomyces cerevisiae. They used this method to measure rates of spontaneous and induced mitotic recombination. Lee et al. have brought increased power to this assay by performing it in diploids with ∼0.5% heterology between the sequences of homologous chromosomes. This design allowed mapping of RCOs at high resolution, and also allowed study of another aspect of recombination—gene conversion (Figure 1C and 1D). Their analysis led to several key findings that provide unique and sometimes surprising insights into questions about mitotic recombination. Figure 1 Reciprocal crossovers and gene conversion.