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An OB-fold complex controls the repair pathways for DNA double-strand breaks

Author

Listed:
  • Shengxian Gao

    (Peking University)

  • Sumin Feng

    (Peking University)

  • Shaokai Ning

    (Peking University)

  • Jingyan Liu

    (Peking University)

  • Huayu Zhao

    (Peking University)

  • Yixi Xu

    (Peking University)

  • Jinfeng Shang

    (Peking University)

  • Kejiao Li

    (Peking University)

  • Qing Li

    (Peking University)

  • Rong Guo

    (Peking University)

  • Dongyi Xu

    (Peking University)

Abstract

53BP1 with its downstream proteins, RIF1, PTIP and REV7, antagonizes BRCA1-dependent homologous recombination (HR) and promotes non-homologous end joining (NHEJ) in an unclear manner. Here we show that REV7 forms a complex with two proteins, FAM35A and C20ORF196. We demonstrate that FAM35A preferentially binds single-strand DNA (ssDNA) in vitro, and is recruited to DSBs as a complex with C20ORF196 and REV7 downstream of RIF1 in vivo. Epistasis analysis shows that both proteins act in the same pathway as RIF1 in NHEJ. The defects in HR pathway to repair DSBs and the reduction in resection of broken DNA ends in BRCA1-mutant cells can be largely suppressed by inactivating FAM35A or C20ORF196, indicating that FAM35A and C20ORF196 prevent end resection in these cells. Together, our data identified a REV7–FAM35A–C20ORF196 complex that binds and protects broken DNA ends to promote the NHEJ pathway for DSB repair.

Suggested Citation

  • Shengxian Gao & Sumin Feng & Shaokai Ning & Jingyan Liu & Huayu Zhao & Yixi Xu & Jinfeng Shang & Kejiao Li & Qing Li & Rong Guo & Dongyi Xu, 2018. "An OB-fold complex controls the repair pathways for DNA double-strand breaks," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06407-7
    DOI: 10.1038/s41467-018-06407-7
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    Cited by:

    1. Yajie Sun & Jeffrey Patterson-Fortin & Sen Han & Zhe Li & Zuzanna Nowicka & Yuna Hirohashi & Susan Kilgas & Jae Kyo Yi & Alexander Spektor & Wojciech Fendler & Panagiotis A. Konstantinopoulos & Dipanj, 2024. "53BP1 loss elicits cGAS-STING-dependent antitumor immunity in ovarian and pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Sumin Feng & Sai Ma & Kejiao Li & Shengxian Gao & Shaokai Ning & Jinfeng Shang & Ruiyuan Guo & Yingying Chen & Britny Blumenfeld & Itamar Simon & Qing Li & Rong Guo & Dongyi Xu, 2022. "RIF1-ASF1-mediated high-order chromatin structure safeguards genome integrity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Inés Paniagua & Zainab Tayeh & Mattia Falcone & Santiago Hernández Pérez & Aurora Cerutti & Jacqueline J. L. Jacobs, 2022. "MAD2L2 promotes replication fork protection and recovery in a shieldin-independent and REV3L-dependent manner," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Estelle Vincendeau & Wenming Wei & Xuefei Zhang & Cyril Planchais & Wei Yu & Hélène Lenden-Hasse & Thomas Cokelaer & Juliana Pipoli da Fonseca & Hugo Mouquet & David J. Adams & Frederick W. Alt & Step, 2022. "SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Kenneth Bødkter Schou & Samuel Mandacaru & Muhammad Tahir & Nikola Tom & Ann-Sofie Nilsson & Jens S. Andersen & Matteo Tiberti & Elena Papaleo & Jiri Bartek, 2024. "Exploring the structural landscape of DNA maintenance proteins," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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