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DNA polymerase stalling, sister chromatid recombination and the BRCA genes

Oncogene volume 19, pages 6176–6183 (2000)Cite this article

Abstract

Heritable predisposition to breast and/or ovarian cancer is determined, in part, by germline mutation affecting one of two tumor suppressor genes, BRCA1 and BRCA2 (Miki et al., 1994; Wooster et al., 1995). These genes are required for the maintenance of genomic integrity and for control of homologous recombination in somatic and meiotic cells. Here, we explore the hypothesis that a major role of the BRCA gene products in the somatic DNA damage response centers upon the control of recombination between sister chromatids during S phase. By analogy with model organisms, we suggest that stalling of a mammalian DNA polymerase complex by its encounter with abnormal DNA structure calls forth a series of responses that collaborate to enforce appropriate recombinational outcomes, and to suppress inappropriate or ‘illegitimate’ recombination.

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Acknowledgements

We would like to thank many colleagues for their generous contributions of thoughts and ideas to this review. In particular, we are grateful to Drs David Livingston, Marila Cordero-Stone, Kenneth Marians and Ian Hickson for helpful discussions. We thank Drs Martin Gellert, William Bonner, Robert Abraham and Randal Tibbetts for sharing data prior to publication. This work was supported by an NIH Howard Temin Award to R Scully.

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  1. Dana Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, Massachusetts, USA

    Ralph Scully, Nadine Puget & Katerina Vlasakova

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Scully, R., Puget, N. & Vlasakova, K. DNA polymerase stalling, sister chromatid recombination and the BRCA genes. Oncogene 19, 6176–6183 (2000). https://doi.org/10.1038/sj.onc.1203971

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