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Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation

Oncogene volume 22, pages 5784–5791 (2003)Cite this article

Abstract

Inheritance of one defective copy of either of the two breast cancer susceptibility genes, BRCA1 and BRCA2, predisposes individuals to breast and ovarian cancers. Current progress in determining the function of these genes suggests that they participate in a common pathway to facilitate orderly homologous recombination and thereby maintain genomic integrity. As a consequence of this defect in homologous recombination, tumors that arise in BRCA carriers are likely to be more sensitive to ionizing radiation. This review summarizes recent investigations about the nature of the defect in DNA repair, and highlights the unanswered questions about the tumor suppressor paradox of BRCA genes. The unsolved mystery is the other genetic changes that must occur to turn a BRCA-deficient cell from a nonviable cell into a tumor cell capable of endless growth.

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  1. Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA

    Simon N Powell

  2. Department of Radiation Oncology, Boston Medical Center, Boston, MA, USA

    Lisa A Kachnic

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Correspondence to Simon N Powell.

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Powell, S., Kachnic, L. Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene 22, 5784–5791 (2003). https://doi.org/10.1038/sj.onc.1206678

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