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Werner and Bloom helicases are involved in DNA repair in a complementary fashion

Oncogene volume 21, pages 954–963 (2002)Cite this article

Abstract

Werner syndrome (WS) is a recessive disorder characterized by premature senescence. Bloom syndrome (BS) is a recessive disorder characterized by short stature and immunodeficiency. A common characteristic of both syndromes is genomic instability leading to tumorigenesis. WRN and BLM genes causing WS and BS, encode proteins that are closely related to the RecQ helicase. We produced WRN−/−, BLM−/− and WRN−/−/BLM−/− mutants in the chicken B-cell line DT40. WRN−/− cells showed hypersensitivities to genotoxic agents, such as 4-nitroquinoline 1-oxide, camptothecin and methyl methanesulfonate. They also showed a threefold increase in targeted integration rate of exogenous DNAs, but not in sister chromatid exchange (SCE) frequency. BLM−/− cells showed hypersensitivities to the genotoxic agents as well as ultraviolet (UV) light, in addition to a 10-fold increase in targeted integration rate and an 11-fold increase in SCE frequency. In WRN−/−/BLM−/− cells, synergistically increased hypersensitivities to the genotoxic agents were observed whereas both SCE frequencies and targeted integration rates were partially diminished compared to the single mutants. Chromosomal aberrations were also synergistically increased in WRN−/−/BLM−/− cells when irradiated with UV light in late S to G2 phases. These results suggest that both WRN and BLM may be involved in DNA repair in a complementary fashion.

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Acknowledgements

We thank Eiichiro Sonoda at Kyoto University and Minoru Takata at Kawasaki Medical School for their valuable technical advice. We also thank Dr William Brown at Oxford University for his generous gift of the chicken HPRT targeting construct. We would like to acknowledge Martin Lavin at Queensland Institute of Medical Research in Australia for critically reading the manuscript. This work was supported by the Drug Organization supervised by the Ministry of Health and Welfare of the Japanese Government.

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  1. Osamu Imamura

    Present address: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, 91125, California, USA

Authors and Affiliations

  1. AGENE Research Institute, 200 Kajiwara, Kamakura, Kanagawa, 247-0063, Japan

    Osamu Imamura, Kumiko Fujita, Chie Itoh, Yasuhiro Furuichi & Takehisa Matsumoto

  2. Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Konoe Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan

    Shunichi Takeda

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Correspondence to Takehisa Matsumoto.

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Imamura, O., Fujita, K., Itoh, C. et al. Werner and Bloom helicases are involved in DNA repair in a complementary fashion. Oncogene 21, 954–963 (2002). https://doi.org/10.1038/sj.onc.1205143

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