Repair of DNA loops involves DNA-mismatch and nucleotide-excision repair proteins

A number of enzymes recognize and repair DNA lesions1. The DNA-mismatch repair system corrects base–base mismatches andsmall loops, whereas the nucleotide-excision repair systemremoves pyrimidine dimers and other helix-distorting lesions. DNA molecules with mismatches or loops can arise as aconsequence of heteroduplex formation during meiotic recombination2. In the yeast Saccharomyces cerevisiae, repair of mismatches results in gene conversion or restoration, and failure to repair the mismatch results in post-meiotic segregation (PMS) (Fig. 1). The ratio of gene-conversion to PMS events reflects the efficiency of DNA repair3,4. By examining the PMS patterns in yeast strains heterozygous for a mutant allele with a 26-base-pair insertion, we find that the repair of 26-base loops involves Msh2 (a DNA-mismatch repair protein) and Rad1 (a protein required for nucleotide-excision repair). Figure 1 Heteroduplex formation and DNA-mismatch repair during meiosis. Paired meiotic chromosomes are shown, with each chromosome being double-stranded. Centromeres are indicated by black and white ovals; rectangles depict genes with mutant insertions shown in black. a, Tetrads in which a wild-type strand is non-reciprocally donated to a mutant gene, or b, in which a mutant DNA strand is non-reciprocally donated to a wild-type gene4. The resulting heteroduplexes contain DNA loops, representing sequences present in the mutant gene but absent in the wild-type gene. Repair of the mismatches can occur either by excision of the loop (followed by resynthesis using the wild-type strand as a template), or by excision of the sequences opposite the loop (followed by resynthesis using the mutant strand as a template). Failure to repair the loop leads to 5 : 3 or 3 : 5 postmeiotic segregation (PMS).