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53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers

Nature Structural and Molecular Biology, ISSN: 1545-9985, Vol: 17, Issue: 6, Page: 688-695
2010
  • 798
    Citations
  • 0
    Usage
  • 695
    Captures
  • 5
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    798
  • Captures
    695
  • Mentions
    5
    • News Mentions
      3
      • 3
    • References
      2
      • 2

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Nature, Published online: 11 September 2024; doi:10.1038/s41586-024-07909-9 BRCA1–BARD1 directly promotes double-strand break repair by stimulating long-range DNA end resection pathways.

Article Description

Germ-line mutations in breast cancer 1, early onset (BRCA1) result in predisposition to breast and ovarian cancer. BRCA1-mutated tumors show genomic instability, mainly as a consequence of impaired recombinatorial DNA repair. Here we identify p53-binding protein 1 (53BP1) as an essential factor for sustaining the growth arrest induced by Brca1 deletion. Depletion of 53BP1 abrogates the ATM-dependent checkpoint response and G2 cell-cycle arrest triggered by the accumulation of DNA breaks in Brca1-deleted cells. This effect of 53BP1 is specific to BRCA1 function, as 53BP1 depletion did not alleviate proliferation arrest or checkpoint responses in Brca2-deleted cells. Notably, loss of 53BP1 partially restores the homologous-recombination defect of Brca1-deleted cells and reverts their hypersensitivity to DNA-damaging agents. We find reduced 53BP1 expression in subsets of sporadic triple-negative and BRCA-associated breast cancers, indicating the potential clinical implications of our findings. © 2010 Nature America, Inc. All rights reserved.

Bibliographic Details

Bouwman, Peter; Aly, Amal; Escandell, Jose M; Pieterse, Mark; Bartkova, Jirina; van der Gulden, Hanneke; Hiddingh, Sanne; Thanasoula, Maria; Kulkarni, Atul; Yang, Qifeng; Haffty, Bruce G; Tommiska, Johanna; Blomqvist, Carl; Drapkin, Ronny; Adams, David J; Nevanlinna, Heli; Bartek, Jiri; Tarsounas, Madalena; Ganesan, Shridar; Jonkers, Jos

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

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