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Conserved domains in the chicken homologue of BRCA2

Oncogene volume 21, pages 1130–1134 (2002)Cite this article

Abstract

Germline mutation of the BRCA2 gene causes a high risk of developing breast and ovarian cancer. Although the BRCA2 protein has been implicated in homologous recombination (HR) of DNA and in transcription, it is still unclear how mutation leads to tumorigenesis. We have identified a non-mammalian homologue of BRCA2 from chicken, which encodes a protein with 3397 amino acids (aa) and shows only 40% identity to human BRCA2. However, comparison of the mammalian and chicken sequences revealed remarkably high homology in several segments. These include a N-terminal region (∼100 aa), which was previously shown to possess intrinsic transcriptional activity, and a C-terminal region (aa residue ∼2480-∼3180 in human BRCA2), which has not been clearly assigned any function. In contrast, although the eight BRC repeats of mammalian BRCA2 are believed to play an important role in HR by interacting with Rad51, the BRC3, BRC5, and BRC6 repeats exhibit virtually no similarity to their mammalian counterparts. Among 311 missense mutations listed as unclassified variants in the NIH Breast Cancer Information Core database, only 83 of these sites are identical in chicken BRCA2. Thus, chicken BRCA2 may provide a means to identify domains and residues associated with cancer predisposition.

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Acknowledgements

The authors would like to thank Y Sato, M Nagao, M Fujii, and M Kimura for their expert technical assistance and thank Drs AR Venkitaraman (University of Cambridge), ME Moynahan (Sloan-Kettering Institute), and D Bishop (University of Chicago) for critical reading of the manuscript and helpful discussion. Financial support was provided in part by CREST.JST. (Saitama, Japan) and Grants-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (M Takata and S Takeda) and from the Ministry of Health, Labour and Welfare of Japan (M Takata). The work was also supported by grants from The Osaka Cancer Research Foundation. A portion of this work was done at LLNL under the auspices of the US Department of Energy under contract No. W-7405-ENG-48.

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Author notes

  1. Seiji Tachiiri

    Present address: Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo, 108-8639, Japan

  2. Minoru Takata and Seiji Tachiiri: M Takata and S Tachiiri contributed equally to this work

Authors and Affiliations

  1. Department of Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan

    Minoru Takata

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

    Minoru Takata, Seiji Tachiiri, Akira Fujimori, Shunichi Takeda & Mitsuyoshi Yamazoe

  3. Department of Therapeutic Radiology and Oncology, Kyoto University School of Medicine, Shogoin-Kawaracho, Sakyo-ku, Kyoto, 606-8507, Japan

    Seiji Tachiiri & Masahiro Hiraoka

  4. CREST, JST, Saitama, Japan

    Akira Fujimori, Shunichi Takeda & Mitsuyoshi Yamazoe

  5. BBR Program, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California, 94551-0808, CA, USA

    Larry H Thompson

  6. Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo, 170-8640, Japan

    Yoshio Miki

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Correspondence to Minoru Takata.

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Takata, M., Tachiiri, S., Fujimori, A. et al. Conserved domains in the chicken homologue of BRCA2. Oncogene 21, 1130–1134 (2002). https://doi.org/10.1038/sj.onc.1205168

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