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DNA methyltransferase Dnmt1 and mismatch repair

Oncogene volume 23, pages 7898–7902 (2004)Cite this article

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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References

  • Bestor TH . (1992). EMBO J., 11, 2611–2617.

  • Bhattacharyya NP, Skandalis A, Ganesh A, Groden J and Meuth M . (1994). Proc. Natl. Acad. Sci. USA, 91, 6319–6323.

  • Chen RZ, Pettersson U, Beard C, Jackson-Grusby L and Jaenisch R . (1998). Nature, 395, 89–93.

  • Chuang LS-H, Ian H-I, Koh T-W, Ng H-H, Xu G and Li BFL . (1997). Science, 277, 1996–2000.

  • Edelmann W, Yang K, Umar A, Heyer J, Lau K, Fan K, Liedtke W, Cohen PE, Kane MF, Lipford JR, Yu N, Crouse GF, Pollard JW, Kunkel T, Lipkin M, Kolodner R and Kucherlapati R . (1997). Cell, 91, 467–477.

  • Eden A, Gaudet F, Waghmare A and Jaenisch R . (2003). Science, 300, 455.

  • Gu L, Hong Y, McCulloch S, Watanabe H and Li G-M . (1998). Nucleic Acids Res., 26, 1173–1178.

  • Guo G, Wang W and Bradley A . (2004). Nature, 429, 891–895.

  • Hare JT and Taylor JH . (1985). Proc. Natl. Acad. Sci. USA, 82, 7350–7354.

  • Hofseth LJ, Khan MA, Ambrose M, Nikolayeva O, Xu-Welliver M, Kartalou M, Hussain SP, Roth RB, Zhou X, Mechanic LE, Zurer I, Rotter V, Samson LD and Harris CC . (2003). J. Clin. Invest., 112, 1887–1894.

  • Holmes Jr J, Clark S and Modrich P . (1990). Proc. Natl. Acad. Sci. USA, 87, 5837–5841.

  • Jackson-Grusby L, Beard C, Possemato R, Tudor M, Fambrough D, Csankovszki G, Dausman J, Lee P, Wilson C, Lander E and Jaenisch R . (2001). Nat. Genet., 27, 31–39.

  • Jiricny J . (1998). EMBO J., 17, 6427–6436.

  • Kabbarah O, Mallon MA, Pfeifer JD, Edelmann W, Kucherlapati R and Goodfellow PJ . (2003). Mol. Carcinogen., 38, 155–159.

  • Kolodner RD . (1995). Trends Biochem. Sci., 20, 397–401.

  • Lei H, Oh SP, Okano M, Jüttermann R, Goss KA, Jaenisch R and Li E . (1996). Development, 122, 3195–3205.

  • Leonhardt H, Page AW, Weier H-U and Bestor TH . (1992). Cell, 71, 865–873.

  • Li E . (2002). Nat. Rev. Genet., 3, 662–673.

  • Lipkin SM, Wang V, Jacoby R, Banerjee-Basu S, Baxevanis AD, Lynch HT, Elliott RM and Collins FS . (2000). Nat. Genet., 24, 27–35.

  • Liu Y, Oakeley EJ, Sun L and Jost J-P . (1998). Nucleic Acids Res., 26, 1038–1045.

  • Luria SE and Delbrück M . (1943). Genetics, 28, 491–511.

  • Milutinovic S, Zhuang Q, Niveleau A and Szyf M . (2003). J. Biol. Chem., 278, 14985–14995.

  • Modrich P and Lahue R . (1996). Annu. Rev. Biochem., 65, 101–133.

  • Okano M, Bell DW, Haber DA and Li E . (1999). Cell, 99, 247–257.

  • Parsons R, Li G-M, Longley M, Modrich P, Liu B, Berk T, Hamilton SR, Kinzler KW and Vogelstein B . (1995). Science, 268, 738–740.

  • Prolla TA, Baker SM, Harris AC, Tsao J-L, Yao X, Bronner CE, Zheng B, Gordon M, Reneker J, Arnheim N, Shibata D, Bradley A and Liskay RM . (1998). Nat. Genet., 18, 276–279.

  • Rountree MR, Bachman KE and Baylin SB . (2000). Nat. Genet., 25, 269–277.

  • Sia EA, Jinks-Robertson S and Petes TD . (1997). Mutat. Res., 383, 61–70.

  • Slupphaug G, Kavli B and Krokan HE . (2003). Mutat. Res., 531, 231–251.

  • Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M, Weijenberg MP, Herman JG and Baylin SB . (2002). Nat. Genet., 31, 141–149.

  • Thomas DC, Roberts JD and Kunkel TA . (1991). J. Biol. Chem., 266, 3744–3751.

  • Umar A, Buermeyer AB, Simon JA, Thomas DC, Clark AB, Liskay RM and Kunkel TA . (1996). Cell, 87, 65–73.

  • Vertino PM, Sekowski JA, Coll JM, Applegren N, Han S, Hickey RJ and Malkas LH . (2002). Cell Cycle, 1, 416–423.

  • Wong E, Yang K, Kuraguchi M, Werling U, Avdievich E, Fan K, Fazzari M, Jin B, Brown AMC, Lipkin M and Edelmann W . (2002). Proc. Natl. Acad. Sci. USA, 99, 14937–14942.

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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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  1. Institute of Genetics, National Yang Ming University, Shih-Pai, Taipei, 112, ROC, Taiwan

    Keh-Yang Wang & C-K James Shen

  2. Institute of Molecular Biology, Academia Sinica, Nan-Kang, Taipei, 115, ROC, Taiwan

    Keh-Yang Wang & C-K James Shen

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  1. Keh-Yang Wang
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Correspondence to C-K James Shen.

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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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