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Identification of a ≦600-kb region on human chromosome 1q42.3 inducing cellular senescence

Oncogene volume 22, pages 281–290 (2003)Cite this article

Abstract

The introduction of a human chromosome 1 via microcell-mediated chromosome transfer (MMCT) induces the cellular senescence in mouse melanoma B16-F10 cells. The senescent cells maintained still the telomerase activity, which is frequently associated with immortal growth of human cells, suggesting that a telomerase-independent mechanism is involved in the senescence observed in this mouse cell line. To map the senescence-inducing gene to a specific chromosomal region, we took two experimental approaches: identification of a minimal region with the senescence-inducing activity via MMCT of a series of subchromosomal transferrable fragments (STFs), each consisting of a different profile of human chromosome 1-derived regions, and identification of a region commonly deleted from the transferred chromosome 1 in the revertant clones that escaped cellular senescence. These approaches identified a 2.7–3.0 Mb of senescence-inducing region shared among the active STFs and a 2.4–3.0 Mb of commonly deleted region in the revertant clones. These two regions overlapped each other to map the responsible gene at the 450 to 600-kb interval between UniSTS93710 and D1S3542 on chromosome 1q42.3. This study provides essential information and materials for cloning and characterization of a novel senescence-inducing gene that functions in a telomerase-independent pathway, which is likely to be conserved between mice and humans.

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Acknowledgements

We thank Lois A Annab and Cynthia A Afshari for valuable comments and suggestions. This study was supported by a Grant-in-Aid for the Second Comprehensive 10-year Strategy for Cancer Control from Ministry of Health, Labour and Welfare of Japan and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. Department of Molecular and Cell Genetics, Faculty of Medicine, School of Life Sciences, Tottori University, Tottori, Japan

    Toshio Yawata, Hiroki Kamino, Hiroyuki Kugoh & Mitsuo Oshimura

  2. Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892, MD, USA

    Toshio Yawata, Izumi Horikawa & J Carl Barrett

  3. Department of Human Genome Science, Life Sciences Division, Graduate School of Medicine, Tottori University, Tottori, Japan

    Motonobu Katoh & Mitsuo Oshimura

  4. Kazusa DNA Research Institute, Kisarazu, Chiba, Japan

    Nobuo Nomura & Michio Oishi

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  1. Toshio Yawata
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  2. Hiroki Kamino
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Correspondence to Mitsuo Oshimura.

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Yawata, T., Kamino, H., Kugoh, H. et al. Identification of a ≦600-kb region on human chromosome 1q42.3 inducing cellular senescence. Oncogene 22, 281–290 (2003). https://doi.org/10.1038/sj.onc.1206143

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  • DOI: https://doi.org/10.1038/sj.onc.1206143

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