In search of the tumour-suppressor functions of BRCA1 and BRCA2

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Abstract

Hereditary breast and ovarian cancer syndromes can be caused by loss-of-function germline mutations in one of two tumour-suppressor genes, BRCA1 and BRCA2 (ref. 1). Each gene product interacts with recombination/DNA repair proteins in pathways that participate in preserving intact chromosome structure. However, it is unclear to what extent such functions specifically suppress breast and ovarian cancer. Here we analyse what is known of BRCA gene function and highlight some unanswered questions in the field.

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Figure 1: Structure and localization of BRCA proteins.
Figure 2: Checkpoint inactivation and BRCA gene-mediated tumorigenesis.
Figure 3: Proposed role for the BRCA proteins in sister chromatid recombination.

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Acknowledgements

We thank many colleagues for stimulating discussions and for sharing data before publication. In particular, J. Feunteun, R. Tibbetts, R. Abraham, W. Bonner, M. Gellert and P. Adams.

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Correspondence to Ralph Scully.

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