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Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR

Author

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  • Yaxin Dai

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Aili Zhang

    (Cleveland Clinic Lerner Research Institute)

  • Shan Shan

    (Chinese Academy of Sciences)

  • Zihua Gong

    (Cleveland Clinic Lerner Research Institute)

  • Zheng Zhou

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

P53-binding protein 1 (53BP1) regulates the double-strand break (DSB) repair pathway choice. A recently identified 53BP1-binding protein Tudor-interacting repair regulator (TIRR) modulates the access of 53BP1 to DSBs by masking the H4K20me2 binding surface on 53BP1, but the underlying mechanism remains unclear. Here we report the 1.76-Å crystal structure of TIRR in complex with 53BP1 tandem Tudor domain. We demonstrate that the N-terminal region (residues 10–24) and the L8-loop of TIRR interact with 53BP1 Tudor through three loops (L1, L3, and L1′). TIRR recognition blocks H4K20me2 binding to 53BP1 Tudor and modulates 53BP1 functions in vivo. Structure comparisons identify a TIRR histidine (H106) that is absent from the TIRR homolog Nudt16, but essential for 53BP1 Tudor binding. Remarkably, mutations mimicking TIRR binding modules restore the disrupted binding of Nudt16-53BP1 Tudor. Our studies elucidate the mechanism by which TIRR recognizes 53BP1 Tudor and functions as a cellular inhibitor of the histone methyl-lysine readers.

Suggested Citation

  • Yaxin Dai & Aili Zhang & Shan Shan & Zihua Gong & Zheng Zhou, 2018. "Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04557-2
    DOI: 10.1038/s41467-018-04557-2
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    Cited by:

    1. Susan Kilgas & Aleem Syed & Patrick Toolan-Kerr & Michelle L. Swift & Shrabasti Roychoudhury & Aniruddha Sarkar & Sarah Wilkins & Mikayla Quigley & Anna R. Poetsch & Maria Victoria Botuyan & Gaofeng C, 2024. "NEAT1 modulates the TIRR/53BP1 complex to maintain genome integrity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Gaofeng Cui & Maria Victoria Botuyan & Pascal Drané & Qi Hu & Benoît Bragantini & James R. Thompson & David J. Schuller & Alexandre Detappe & Michael T. Perfetti & Lindsey I. James & Stephen V. Frye &, 2023. "An autoinhibited state of 53BP1 revealed by small molecule antagonists and protein engineering," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Sameer Bikram Shah & Youhang Li & Shibo Li & Qing Hu & Tong Wu & Yanmeng Shi & Tran Nguyen & Isaac Ive & Linda Shi & Hailong Wang & Xiaohua Wu, 2024. "53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR)," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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