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  • Original Paper
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Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells

Oncogene volume 20, pages 1143–1151 (2001)Cite this article

Abstract

Bloom syndrome (BS) is a recessive human genetic disorder characterized by short stature, immunodeficiency and an elevated risk of malignancy. The gene mutated in BS, BLM, encodes a RecQ-type DNA helicase. BS cells have mutator phenotypes such as hyper-recombination, chromosome instability and an increased frequency of sister chromatid exchange (SCE). To define the primary role of BLM, we generated BLM−/− mutants of the chicken B-cell line DT40. In addition to characteristics of BLM−/− cells reported previously by the other group, they are hypersensitive to genotoxic agents such as etoposide, bleomycin and 4-nitroquinoline-1-oxide and irradiation with the short wave length of UV (UVC) light, whereas they exhibit normal sensitivity to X-ray irradiation and hydroxyurea. UVC irradiation to BLM−/− cells during G1 to early S phase caused chromosomal instability such as chromatid breaks and chromosomal quadriradials, leading to eventual cell death. These results suggest that BLM is involved in surveillance of base abnormalities in genomic DNA that may be encountered by replication forks in early S phase. Such surveillance would maintain genomic stability in vertebrate cells, resulting in the prevention of cellular tumorigenesis.

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Acknowledgements

We thank Chie Itoh for her technical assistance. We also thank Eiichiro Sonoda and Minoru Takata at Kyoto University for their valuable technical advice. We would like to acknowledge Martin Lavin at Queensland Institute of Medical Research in Australia for critically reading the manuscript. We thank Nathan A Ellis for kindly providing plasmids for expression of wild-type and ATPase-defective HsBLMs. 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. AGENE Research Institute, 200 Kajiwara, Kamakura, 247-0063, Kanagawa, Japan

    Osamu Imamura, Kumiko Fujita, Akira Shimamoto, Yasuhiro Furuichi & Takehisa Matsumoto

  2. Division of Genetics and Mutagenesis, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo, 158-8501, Japan

    Hideyuki Tanabe

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

    Shunichi Takeda

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  1. Osamu Imamura
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Imamura, O., Fujita, K., Shimamoto, A. et al. Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells. Oncogene 20, 1143–1151 (2001). https://doi.org/10.1038/sj.onc.1204195

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