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A second DNA binding site in human BRCA2 promotes homologous recombination

Author

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  • Catharina von Nicolai

    (Institut Curie, PSL Research University, UMR 3348, Genotoxic Stress and Cancer Unit, Research Center, Paris Sud University, Paris Saclay University, Centre Universitaire d’Orsay, Bâtiment 110)

  • Åsa Ehlén

    (Institut Curie, PSL Research University, UMR 3348, Genotoxic Stress and Cancer Unit, Research Center, Paris Sud University, Paris Saclay University, Centre Universitaire d’Orsay, Bâtiment 110)

  • Charlotte Martin

    (Institut Curie, PSL Research University, UMR 3348, Genotoxic Stress and Cancer Unit, Research Center, Paris Sud University, Paris Saclay University, Centre Universitaire d’Orsay, Bâtiment 110)

  • Xiaodong Zhang

    (Imperial College London)

  • Aura Carreira

    (Institut Curie, PSL Research University, UMR 3348, Genotoxic Stress and Cancer Unit, Research Center, Paris Sud University, Paris Saclay University, Centre Universitaire d’Orsay, Bâtiment 110)

Abstract

BRCA2 tumour-suppressor protein is well known for its role in DNA repair by homologous recombination (HR); assisting the loading of RAD51 recombinase at DNA double-strand breaks. This function is executed by the C-terminal DNA binding domain (CTD) which binds single-stranded (ss)DNA, and the BRC repeats, which bind RAD51 and modulate its assembly onto ssDNA. Paradoxically, analysis of cells resistant to DNA damaging agents missing the CTD restore HR proficiency, suggesting another domain may take over its function. Here, we identify a region in the N terminus of BRCA2 that exhibits DNA binding activity (NTD) and provide evidence for NTD promoting RAD51-mediated HR. A missense variant detected in breast cancer patients located in the NTD impairs HR stimulation on dsDNA/ssDNA junction containing substrates. These findings shed light on the function of the N terminus of BRCA2 and have implications for the evaluation of breast cancer variants.

Suggested Citation

  • Catharina von Nicolai & Åsa Ehlén & Charlotte Martin & Xiaodong Zhang & Aura Carreira, 2016. "A second DNA binding site in human BRCA2 promotes homologous recombination," Nature Communications, Nature, vol. 7(1), pages 1-8, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12813
    DOI: 10.1038/ncomms12813
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    Cited by:

    1. Domagoj Vugic & Isaac Dumoulin & Charlotte Martin & Anna Minello & Lucia Alvaro-Aranda & Jesus Gomez-Escudero & Rady Chaaban & Rana Lebdy & Catharina Nicolai & Virginie Boucherit & Cyril Ribeyre & Ang, 2023. "Replication gap suppression depends on the double-strand DNA binding activity of BRCA2," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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