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Interaction between BRCA2 and replication protein A is compromised by a cancer-predisposing mutation in BRCA2

Oncogene volume 22, pages 28–33 (2003)Cite this article

Abstract

Mutations in the BRCA1 and BRCA2 genes predispose women to familial, early-onset breast cancer. Both the BRCA1 and BRCA2 proteins appear to function in the homologous recombination pathway of DNA double-strand break repair. Both BRCA1 and BRCA2 have also been implicated in transcription by RNA polymerase II, for both proteins have domains which, when tethered adjacent to a promoter, can activate transcription. In experiments reported here, we have used protein affinity chromatography and coimmunoprecipitation techniques to show that the putative N-terminal acidic transcriptional activation domain of BRCA2 interacts with replication protein A (RPA), a protein essential for DNA repair, replication and recombination. This interaction was not mediated by DNA and was specific for human RPA but not yeast RPA. Since the cancer-predisposing mutation Y42C in BRCA2 significantly compromised the interaction between RPA and BRCA2, this interaction may be biologically important. That BRCA2 protein in HeLa cell extract also coimmunoprecipitated with RPA suggested that this interaction occurs in vivo. Therefore, the transcriptional activation domains within BRCA2, and perhaps BRCA1, may provide links to RPA and DNA repair processes rather than transcription.

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Acknowledgements

JMSW (deceased) and DI made equal contributions. We thank Michael Shales for assistance with preparation of the manuscript. This work was supported by a grant to CJI from the National Cancer Institute of Canada with funds from the Canadian Cancer Society.

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Authors and Affiliations

  1. Banting and Best Department of Medical Research, University of Toronto, Toronto, M5G 1L6, Ontario, Canada

    Johnson M S Wong, Daniela Ionescu & C James Ingles

  2. Department of Molecular and Medical Genetics, University of Toronto, Toronto, M5G 1L6, Ontario, Canada

    Daniela Ionescu & C James Ingles

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  1. Johnson M S Wong
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Correspondence to C James Ingles.

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Wong, J., Ionescu, D. & Ingles, C. Interaction between BRCA2 and replication protein A is compromised by a cancer-predisposing mutation in BRCA2. Oncogene 22, 28–33 (2003). https://doi.org/10.1038/sj.onc.1206071

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