Recombination events between non-identical sequences most often involve het
eroduplex DNA intermediates that are subjected to mismatch repair. The well
-characterized long-patch mismatch repair process, controlled in eukaryotes
by bacterial MutS and MutL orthologs, is the major system involved in repa
ir of mispaired bases. Here we present evidence for an alternative short-pa
tch mismatch repair pathway that operates on a broad spectrum of mismatches
. In msh2 mutants lacking the long-patch repair system, sequence analysis o
f recombination tracts resulting from exchanges between similar but non-ide
ntical (homeologous) parental DNAs showed the occurrence of short-patch rep
air events that can involve <12 nucleotides. Such events were detected both
in mitotic and in meiotic recombinants, Confirming the existence of a dist
inct short-patch repair activity, we found in a recombination assay involvi
ng homologous alleles that closely spaced mismatches are repaired independe
ntly with high efficiency in cells lacking MSH2 or PMS1. We show that this
activity does not depend on genes required for nucleotide excision repair a
nd thus differs from the short-patch mismatch repair described in Schizosac
charomyces pombe.