Regulation of mitotic homeologous recombination in yeast: Functions of mismatch repair and nucleotide excision repair genes

The Saccharomyces cerevisiae homologs of the bacterial mismatch repair prot eins MutS and MutL correct replication errors and prevent recombination bet ween homeologous (nonidentical) sequences. Previously, we demonstrated that Msh2p, Msh3p, and Pms1p regulate recombination between 91% identical inver ted repeats, and here use the same substrates to show that Mlh1p and Msh6p have important antirecombination roles. In addition, substrates containing defined types of mismatches (base-base mismatches; 1-, 4-, or 12-nt inser.t ion/deletion loops; or 18-nt palindromes) were used to examine recognition of these mismatches in mitotic recombination intermediates. Msh2p was requi red for recognition of all types of mismatches, whereas Msh6p recognized on ly base-base mismatches and I-nt insertion/deletion loops. Msh3p was involv ed in recognition of the palindrome and all loops, but also had an unexpect ed antirecombination roles when the potential heteroduplex contained only b ase-base mismatches. In contrast to their similar antimutator roles, Pms1p consistently inhibited recombination to a lesser degree than did Msh2p. In addition to the yeast MutS and MutL homologs, the exonuclease Exo1p and the nucleotide excision repair proteins Rad1p and Rad10p were found to have ro les in inhibiting recombination between mismatched substrates.