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Differential regulation of expression of the mammalian DNA repair genes by growth stimulation

Oncogene volume 23, pages 8581–8590 (2004)Cite this article

Abstract

During DNA replication, DNA becomes more vulnerable to certain DNA damages. DNA repair genes involved in repair of the damages may be induced by growth stimulation. However, regulation of DNA repair genes by growth stimulation has not been analysed in detail. In this report, we analysed the regulation of expression of mammalian MSH2, MSH3 and MLH1 genes involved in mismatch repair, and Rad51 and Rad50 genes involved in homologous recombination repair, in relation to cell growth. Unexpectedly, we found a clear difference in regulation of these repair gene expression by growth stimulation even in the same repair system. The expression of MSH2, MLH1 and Rad51 genes was clearly growth regulated, whereas MSH3 and Rad50 genes were constitutively expressed, suggesting differential requirement of the repair gene products for cell proliferation. MSH3 gene is located in a bidirectionally divergent manner with DHFR gene that is regulated by growth stimulation, indicating that bidirectionally divergent promoters are not necessarily coordinately regulated. Promoter analysis showed that the growth-regulated expression of MLH1 and Rad51 genes was mainly mediated by E2F that plays crucial roles in regulation of DNA replication, suggesting close relation between some of the repair genes and DNA replication.

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Acknowledgements

We thank K Maruyama, Y Yuasa, E Ito, Y Iwahashi and Y Yanagisawa for the reporter plasmids. We also thank S Morinaga for excellent technical assistance. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from The Ministry of Education, Culture, Sports, Science and Technology.

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  1. Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Ritsuko Iwanaga, Hideyuki Komori & Kiyoshi Ohtani

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  1. Ritsuko Iwanaga
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Correspondence to Kiyoshi Ohtani.

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Iwanaga, R., Komori, H. & Ohtani, K. Differential regulation of expression of the mammalian DNA repair genes by growth stimulation. Oncogene 23, 8581–8590 (2004). https://doi.org/10.1038/sj.onc.1207976

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