The conversion gradient at HIS4 of Saccharomyces cerevisiae. I. Heteroduplex rejection and restoration of Mendelian segregation

In Saccharomyces cerevisiae, some gene loci manifest gradients in the frequ ency of aberrant segregation in meiosis, with the high end of each gradient corresponding to a hotspot for DNA double-strand breaks (DSBs). The slope of a gradient is reduced when mismatch repair functions fail to act upon he teroduplex DNA-aberrant segregation frequencies at the low end of the gradi ent are higher in the absence of mismatch repair. Two models for the role o f mismatch repair functions in the generation of meiotic "conversion gradie nts" have been proposed. The heteroduplex rejection model suggests that rec ognition of mismatches by mismatch repair enzymes limits hybrid DNA flankin g the site of a DSB. The restoration-conversion model proposes that mismatc h repair does not affect the length of hybrid DNA, but instead increasingly favors restoration of Mendelian segregation over full conversion with incr easing distance from the DSB site. In our experiment designed to distinguis h between these two models, data for one subset of well repairable mismatch es in the HIS4 gene failed to show restoration-type repair but did indicate reduction in the length of hybrid DNA, supporting the heteroduplex rejecti on model. However, another subset of data manifested restoration-type repai r, indicating a relationship between Holliday junction resolution and misma tch repair. We also present evidence for the infrequent formation of symmet ric hybrid DNA during meiotic DSB repair.