MISMATCH REPAIR IN SCHIZOSACCHAROMYCES-POMBE REQUIRES THE MUTL HOMOLOGOUS GENE PMS1 - MOLECULAR-CLONING AND FUNCTIONAL-ANALYSIS

Homologues of the bacterial mutS and mutL genes involved in DNA mismat ch repair have been found in organisms from bacteria to humans. Here, we describe the structure and function of a newly identified Schizosac charomyces pombe gene that encodes a predicted amino acid sequence of 794 residues with a high degree of homology to MutL related proteins. On the basis of its closer relationship to the eukaryotic ''PMS'' gene s than to the ''MLH'' genes, we have designated the S. pombe homologue pms1. Disruption of the pms1 gene causes a significant increase of sp ontaneous mutagenesis as documented by reversion rate measurements. Te trad analyses of crosses homozygous for the pms1 mutation reveal a red uction of spore viability from >92% to 80% associated with a low propo rtion (similar to 50%) of meioses producing four viable spores and a s ignificant, allele-dependent increase of the level of post-meiotic seg regation of genetic marker allele pairs. The mutant phenotypes are con sistent with a general function of pms1 in correction of mismatched ba se pairs arising as a consequence of DNA polymerase errors during DNA synthesis, or of hybrid DNA formation between homologous but not perfe ctly complementary DNA strands during meiotic recombination.