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A cell cycle-dependent BRCA1–UHRF1 cascade regulates DNA double-strand break repair pathway choice

Author

Listed:
  • Haoxing Zhang

    (School of Life Sciences, Southwest University)

  • Hailong Liu

    (State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine)

  • Yali Chen

    (State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine)

  • Xu Yang

    (State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine)

  • Panfei Wang

    (State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine)

  • Tongzheng Liu

    (Mayo Clinic, Rochester)

  • Min Deng

    (Mayo Clinic, Rochester)

  • Bo Qin

    (Mayo Clinic, Rochester)

  • Cristina Correia

    (Mayo Clinic, Rochester)

  • Seungbaek Lee

    (Mayo Clinic, Rochester)

  • Jungjin Kim

    (Mayo Clinic, Rochester)

  • Melanie Sparks

    (Washington University)

  • Asha A. Nair

    (BSI-Genetics & Bioinformatics, Mayo Clinic)

  • Debra L. Evans

    (Mayo Clinic, Rochester)

  • Krishna R. Kalari

    (BSI-Genetics & Bioinformatics, Mayo Clinic)

  • Pumin Zhang

    (Baylor College of Medicine)

  • Liewei Wang

    (Molecular Pharmacology and Experimental therapeutics, Mayo Clinic)

  • Zhongsheng You

    (Washington University)

  • Scott H. Kaufmann

    (Mayo Clinic, Rochester)

  • Zhenkun Lou

    (State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
    Mayo Clinic, Rochester
    Molecular Pharmacology and Experimental therapeutics, Mayo Clinic)

  • Huadong Pei

    (State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine)

Abstract

BRCA1 is an important mediator of the DNA damage response, which promotes homologous recombination (HR) and antagonizes 53BP1-dependent non-homologous end joining in S/G2 phase. But how this is achieved remains unclear. Here, we report that the E3 ubiquitin ligase UHRF1 (Ubiquitin-like, with PHD and RING finger domains 1) directly participates in the interplay between BRCA1 and 53BP1. Mechanistically, UHRF1 is recruited to DNA double-strand breaks (DSBs) by BRCA1 in S phase, which requires the BRCT domain of BRCA1 and phosphorylated Ser674 of UHRF1. Subsequently, UHRF1 mediates K63-linked polyubiquitination of RIF1, and results in its dissociation from 53BP1 and DSBs thereby facilitating HR initiation. Thus, UHRF1 is a key regulator of DSB repair choice, which is separate from its role in heterochromatin formation and epigenetic regulator.

Suggested Citation

  • Haoxing Zhang & Hailong Liu & Yali Chen & Xu Yang & Panfei Wang & Tongzheng Liu & Min Deng & Bo Qin & Cristina Correia & Seungbaek Lee & Jungjin Kim & Melanie Sparks & Asha A. Nair & Debra L. Evans & , 2016. "A cell cycle-dependent BRCA1–UHRF1 cascade regulates DNA double-strand break repair pathway choice," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10201
    DOI: 10.1038/ncomms10201
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    Cited by:

    1. Lianmei Tan & Tao Yin & Handan Xiang & Liuyang Wang & Poorva Mudgal & Junying Chen & Yi Ding & Guoping Wang & Bryan Jian Wei Lim & Yuqi Huang & De Huang & Yaosi Liang & Peter B. Alexander & Kun Xiang , 2024. "Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Kaja Kostyrko & Marta Román & Alex G. Lee & David R. Simpson & Phuong T. Dinh & Stanley G. Leung & Kieren D. Marini & Marcus R. Kelly & Joshua Broyde & Andrea Califano & Peter K. Jackson & E. Alejandr, 2023. "UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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