Abstract
Yeast Msh2p forms complexes with Msh3p and Msh6p to repair DNA mispairs that arise during DNA replication. In addition to their role in mismatch repair (MMR), the
MSH2
and
MSH3
gene products are required to remove 3′ nonhomologous DNA tails during genetic recombination. The mismatch repair genes
MSH6
,
MLH1
, and
PMS1
, whose products interact with Msh2p, are not required in this process. We have identified mutations in
MSH2
that do not disrupt genetic recombination but confer a strong defect in mismatch repair. Twenty-four
msh2
mutations that conferred a dominant negative phenotype for mismatch repair were isolated. A subset of these mutations mapped to residues in Msh2p that were analogous to mutations identified in human nonpolyposis colorectal cancer
msh2
kindreds. Approximately half of the these MMR-defective mutations retained wild-type or nearly wild-type activity for the removal of nonhomologous DNA tails during genetic recombination. The identification of mutations in
MSH2
that disrupt mismatch repair without affecting recombination provides a first step in dissecting the Msh-effector protein complexes that are thought to play different roles during DNA repair and genetic recombination.