We have examined the relationship between DNA mismatch repair and deficiency of DNA methylation in a mouse embryonic cell line, Dnmt1 -/- ES, with homologous deletion of the gene coding for the maintenance DNA methyltransferase Dnmt1. With the use of a sensitive PCR for the assay of two mononucleotide- and three dinucleotide microsatellite markers that exhibited instabilities in mismatch repair-deficient cells, significantly higher frequencies of instability were detected at three of the five markers in Dnmt1-/- ES than the wild-type ES. The data suggest that Dnmt1 enzyme plays an integrating role in DNA replication and/or repair. The implication that Dnmt1 enzyme and/or cytosine methylation may participate in the strand discrimination of mismatch repair during eukaryotic DNA replication is discussed.
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