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BRCA1 and CtIP suppress long-tract gene conversion between sister chromatids

Author

Listed:
  • Gurushankar Chandramouly

    (Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Amy Kwok

    (Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Present address: University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA)

  • Bin Huang

    (Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Nicholas A. Willis

    (Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Anyong Xie

    (Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Ralph Scully

    (Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

Abstract

BRCA1 controls early steps of the synthesis-dependent strand annealing (SDSA) pathway of homologous recombination, but has no known role following Rad51-mediated synapsis. Here we show that BRCA1 influences post-synaptic homologous recombination events, controlling the balance between short- (STGC) and long-tract gene conversion (LTGC) between sister chromatids. Brca1 mutant cells reveal a bias towards LTGC that is corrected by expression of wild-type but not cancer-predisposing BRCA1 alleles. The LTGC bias is enhanced by depletion of CtIP but reversed by inhibition of 53BP1, implicating DNA end resection as a contributor to the STGC/LTGC balance. The impact of BRCA1/CtIP loss on the STGC/LTGC balance is abolished when the second (non-invading) end of the break is unable to support termination of STGC by homologous pairing (annealing). This suggests that BRCA1/CtIP-mediated processing of the second end of the break controls the annealing step that normally terminates SDSA, thereby suppressing the error-prone LTGC outcome.

Suggested Citation

  • Gurushankar Chandramouly & Amy Kwok & Bin Huang & Nicholas A. Willis & Anyong Xie & Ralph Scully, 2013. "BRCA1 and CtIP suppress long-tract gene conversion between sister chromatids," Nature Communications, Nature, vol. 4(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3404
    DOI: 10.1038/ncomms3404
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    Cited by:

    1. Yi-Li Feng & Qian Liu & Ruo-Dan Chen & Si-Cheng Liu & Zhi-Cheng Huang & Kun-Ming Liu & Xiao-Ying Yang & An-Yong Xie, 2022. "DNA nicks induce mutational signatures associated with BRCA1 deficiency," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. J. A. Kamp & B. B. L. G. Lemmens & R. J. Romeijn & S. C. Changoer & R. Schendel & M. Tijsterman, 2021. "Helicase Q promotes homology-driven DNA double-strand break repair and prevents tandem duplications," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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