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DNA mismatch repair (DMR) functions to maintain genome stability. Prokaryotic and eukaryotic cells deficient in DMR show a microsatellite instability (MSI) phenotype characterized by repeat length alterations at microsatellite sequences. Mice deficient in Pms2, a mammalian homolog of bacterial mutL, develop cancer and display MSI in all tissues examined, including the male germ line where a frequency of ~10% was observed. To determine the consequences of maternal DMR deficiency on genetic stability, we analyzed [F.sub.1] progeny from [Pms2.sup.-/-] female mice mated with wild-type males. Our analysis indicates that MSI in the female germ line was ~9%. MSI was also observed in paternal alleles, a surprising result since the alleles were obtained from wild-type males and the embryos were therefore DMR proficient. We propose that mosaicism for paternal alleles is a maternal effect that results from Pms2 deficiency during the early cleavage divisions. The absence of DMR in one-cell embryos leads to the formation of unrepaired replication errors in early cell divisions of the zygote. The occurrence of postzygotic mutation in the early mouse embryo suggests that Pms2 deficiency is a maternal effect, one of a limited number identified in the mouse and the first to involve a DNA repair gene.

DNA mismatch repair gene PMS2 plays a role in DNA mismatch repair in several kinds of tissues. The animals lacking PMS2 seem vulnerable to sarcomas and lymphomas. PMS2 lacking males are impotent and able to produce only abnormal spermatozoa. The investigation of axial element and synaptonemal complex creation during prophase of meiosis I shows abnormalities in chromosome synapsis. These findings indicate relation among mismatch repair, genetic recombination and chromosome synapsis in meiosis.

R. Michael Liskay [1] Sean M. Baker [2] Suzanne M. Deschenes [1] Andrew B. Buermeyer [1] Key Words mutator, hereditary cancer, genetic instability, tumorigenesis, mice * Abstract DNA mismatch repair [...]

A meiotic study was conducted to characterize the recombination defects influenced by the loss of MLH1 protein and to find out the effects of reduced recombination on mammalian female meiotic process. Results suggest that the absence of Mlh1 protein causes signifiant recombination reduction. This recombination defect has been found to promote sterility among Mlh1 mutant females that leads to significant disruptions in the meiotic process.