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Insights into DNA recombination from the structure of a RAD51–BRCA2 complex

Author

Listed:
  • Luca Pellegrini

    (University of Cambridge)

  • David S. Yu

    (University of Cambridge, CR UK Department of Oncology and The Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre)

  • Thomas Lo

    (University of Cambridge)

  • Shubha Anand

    (University of Cambridge, CR UK Department of Oncology and The Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre)

  • MiYoung Lee

    (University of Cambridge, CR UK Department of Oncology and The Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre)

  • Tom L. Blundell

    (University of Cambridge)

  • Ashok R. Venkitaraman

    (University of Cambridge, CR UK Department of Oncology and The Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre)

Abstract

The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a recombinase enzyme, in pathways for DNA repair by homologous recombination. We report here the structure of a complex between an evolutionarily conserved sequence in BRCA2 (the BRC repeat) and the RecA-homology domain of RAD51. The BRC repeat mimics a motif in RAD51 that serves as an interface for oligomerization between individual RAD51 monomers, thus enabling BRCA2 to control the assembly of the RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. The RAD51 oligomerization motif is highly conserved among RecA-like recombinases, highlighting a common evolutionary origin for the mechanism of nucleoprotein filament formation, mirrored in the BRC repeat. Cancer-associated mutations that affect the BRC repeat disrupt its predicted interaction with RAD51, yielding structural insight into mechanisms for cancer susceptibility.

Suggested Citation

  • Luca Pellegrini & David S. Yu & Thomas Lo & Shubha Anand & MiYoung Lee & Tom L. Blundell & Ashok R. Venkitaraman, 2002. "Insights into DNA recombination from the structure of a RAD51–BRCA2 complex," Nature, Nature, vol. 420(6913), pages 287-293, November.
    • Handle: RePEc:nat:nature:v:420:y:2002:i:6913:d:10.1038_nature01230
    DOI: 10.1038/nature01230
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    Cited by:

    1. Robert Appleby & Luay Joudeh & Katie Cobbett & Luca Pellegrini, 2023. "Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. James M. Dunce & Owen R. Davies, 2024. "BRCA2 stabilises RAD51 and DMC1 nucleoprotein filaments through a conserved interaction mode," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Youngho Kwon & Heike Rösner & Weixing Zhao & Platon Selemenakis & Zhuoling He & Ajinkya S. Kawale & Jeffrey N. Katz & Cody M. Rogers & Francisco E. Neal & Aida Badamchi Shabestari & Valdemaras Petrosi, 2023. "DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Manickam Gurusaran & Jingjing Zhang & Kexin Zhang & Hiroki Shibuya & Owen R. Davies, 2024. "MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Yan Wang & Binbin Ma & Xiaoxu Liu & Ge Gao & Zhuanzhuan Che & Menghan Fan & Siyan Meng & Xiru Zhao & Rio Sugimura & Hua Cao & Zhongjun Zhou & Jing Xie & Chengqi Lin & Zhuojuan Luo, 2022. "ZFP281-BRCA2 prevents R-loop accumulation during DNA replication," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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