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BRCA1 gene: function and deficiency

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Abstract

The BRCA1 protein, a hereditary breast and ovarian cancer-causing gene product, is known as a multifunctional protein that performs various functions in cells. It is well known, along with BRCA 2, to cause hereditary breast and ovarian cancer, but here we will specifically focus on BRCA1. We introduce the mechanism and the latest report on homologous recombination repair, replication, involvement in checkpoint regulation, transcription, chromatin remodeling, and cytoplasmic function (centrosome regulation, apoptosis, selective autophagy), and consider the possibility of carcinogenesis from inhibition of the intracellular functions in each. We also consider the possibility of drug development based on each function. Finally, we will explain, from data obtained through basic research, that an appropriate regimen is important for raising the response rate for poly (ADP)-ribose polymerase inhibitors, in the case of low susceptibility, iatrogenic toxicity, tolerance, etc.

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Acknowledgements

We thank all members of the Department of Molecular Genetics of the Tokyo Medical and Dental University who provided helpful discussion.

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Authors and Affiliations

  1. Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Miho Takaoka & Yoshio Miki

  2. Department of Genetic Diagnosis, The Cancer Institute, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Yoshio Miki

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  1. Miho Takaoka
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  2. Yoshio Miki
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Correspondence to Yoshio Miki.

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Yoshio Miki received honoraria from AstraZenaca Co., Ltd. Miho Takaoka has no conflict of interest to disclose.

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Takaoka, M., Miki, Y. BRCA1 gene: function and deficiency. Int J Clin Oncol 23, 36–44 (2018). https://doi.org/10.1007/s10147-017-1182-2

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