Abstract
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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Acknowledgements
We are indebted to Drs Y-S Jou and Peter Tsai at the National Health Research Institute, Taipei, Taiwan for their help on the genotyping experiments. We also thank Drs En Li and Paul Modrich for their critical and helpful comments. Dnmt1−/− ES cell line is a kind gift from Dr En Li. This work was supported by the National Science Council and the Academia Sinica, Taipei, Taiwan, ROC.
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Wang, KY., James Shen, CK. DNA methyltransferase Dnmt1 and mismatch repair. Oncogene 23, 7898–7902 (2004). https://doi.org/10.1038/sj.onc.1208111
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DOI: https://doi.org/10.1038/sj.onc.1208111
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