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BRCA2-dependent and independent formation of RAD51 nuclear foci

Oncogene volume 22, pages 1115–1123 (2003)Cite this article

Abstract

The formation of RAD51 foci in response to ionizing radiation (IR) represents an important step in the repair of DNA double-strand breaks. RAD51 foci also appear during S phase and are thought to be required for the restart of stalled or broken replication forks. The RAD51 recombinase interacts directly with the breast cancer-associated tumour suppressor BRCA2, an interaction that is required for normal recombination proficiency, radiation resistance and genome stability. In CAPAN-1 cells, which express a truncated form of BRCA2 that is cytoplasmic because of loss of the nuclear localization signal, the formation of IR-induced RAD51 foci is impaired. In this work, we show that S-phase RAD51 foci form normally in CAPAN-1 cells expressing truncated BRCA2. Moreover, we find that RAD51 specifically associates with chromatin at S phase in a reaction that is BRCA2-independent. The observed BRCA2-dependent and independent formation of RAD51 foci shows that intact BRCA2 is not required for RAD51 focus formation per se, leading us to suggest that S phase and IR-induced RAD51 foci assemble by distinct pathways with defined protein requirements.

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Acknowledgements

We thank Fumiko Esashi for help with fractionation procedures, Peter Jordan and Daniel Zicha of the ICRF Light Microscopy Unit for their assistance with confocal microscopy, Ruth Peat, Rachel Horton-Harpin and Chris Saunders of the ICRF Cell Services Unit for tissue culture, and Rick Wood, Jim Ingles and Alain Verreault for the gift of antibodies. We also thank members of the laboratory for their comments. This work was supported by Cancer Research UK and the Swiss Bridge Foundation. MT is supported in part by a fellowship from the European Molecular Biology Organisation.

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  1. Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, EN6 3LD, Herts, UK

    Madalena Tarsounas & Stephen C West

  2. 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Derek Davies

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  1. Madalena Tarsounas
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Correspondence to Stephen C West.

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Tarsounas, M., Davies, D. & West, S. BRCA2-dependent and independent formation of RAD51 nuclear foci. Oncogene 22, 1115–1123 (2003). https://doi.org/10.1038/sj.onc.1206263

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