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Gene silencing in phenomena related to DNA repair

Oncogene volume 21, pages 9033–9042 (2002)Cite this article

Abstract

DNA methylation is essential for embryonic development and important for transcriptional repression, as observed in several biological phenomena. These include genomic imprinting, X-inactivation and carcinogenesis. The basic mechanism by which DNA methlyation silences transcription is generally understood, but there is still much to be learned about how DNA methyltransferase is targeted to a specific region of the gene. Silencing by DNA methylation occurs at an early stage of carcinogenesis, when the DNA repair genes, MGMT and hMLH1, are frequently inactivated, resulting in mutations in key cancer-related genes in cells. Mice defective in Mgmt and/or Mlh1 gave clear evidence of the significant roles of these proteins in carcinogenesis. Recently, it has been demonstrated that DNA methylation is linked to histone methylation in fungi and plants, although it remains unknown whether this mechanism occurs in mammalian systems.

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Acknowledgements

We thank Drs S Matsukura, Y Satoh, T Nakagawachi and H Yatsuki for helping us to collect data. We also thank Drs H Soejima and S Matsukura for useful discussions.

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Authors and Affiliations

  1. Division of Molecular Biology and Genetics, Department of Biomolecular Sciences, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Tsunehiro Mukai

  2. Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, 565-0874, Osaka, Japan

    Mutsuo Sekiguchi

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  1. Tsunehiro Mukai
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Correspondence to Tsunehiro Mukai.

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Mukai, T., Sekiguchi, M. Gene silencing in phenomena related to DNA repair. Oncogene 21, 9033–9042 (2002). https://doi.org/10.1038/sj.onc.1206095

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