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Crosstalk between SUMOylation and ubiquitylation controls DNA end resection by maintaining MRE11 homeostasis on chromatin

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  • Tao Zhang

    (Peking University Health Science Center)

  • Han Yang

    (Peking University Health Science Center)

  • Zenan Zhou

    (Peking University Health Science Center)

  • Yongtai Bai

    (Peking University Health Science Center)

  • Jiadong Wang

    (Peking University Health Science Center)

  • Weibin Wang

    (Peking University Health Science Center)

Abstract

DNA end resection is delicately regulated through various types of post-translational modifications to initiate homologous recombination, but the involvement of SUMOylation in this process remains incompletely understood. Here, we show that MRE11 requires SUMOylation to shield it from ubiquitin-mediated degradation when resecting damaged chromatin. Upon DSB induction, PIAS1 promotes MRE11 SUMOylation on chromatin to initiate DNA end resection. Then, MRE11 is deSUMOylated by SENP3 mainly after it has moved away from DSB sites. SENP3 deficiency results in MRE11 degradation failure and accumulation on chromatin, causing genome instability. We further show that cancer-related MRE11 mutants with impaired SUMOylation exhibit compromised DNA repair ability. Thus, we demonstrate that MRE11 SUMOylation in coordination with ubiquitylation is dynamically controlled by PIAS1 and SENP3 to facilitate DNA end resection and maintain genome stability.

Suggested Citation

  • Tao Zhang & Han Yang & Zenan Zhou & Yongtai Bai & Jiadong Wang & Weibin Wang, 2022. "Crosstalk between SUMOylation and ubiquitylation controls DNA end resection by maintaining MRE11 homeostasis on chromatin," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32920-x
    DOI: 10.1038/s41467-022-32920-x
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    Cited by:

    1. Bing-Ze Yang & Mei-Yin Liu & Kuan-Lin Chiu & Yuh-Ling Chien & Ching-An Cheng & Yu-Lin Chen & Li-Yu Tsui & Keng-Ru Lin & Hsueh-Ping Catherine Chu & Ching-Shyi Peter Wu, 2024. "DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Richa B. Shah & Yuanyuan Li & Honglin Yu & Ela Kini & Samuel Sidi, 2024. "Stepwise phosphorylation and SUMOylation of PIDD1 drive PIDDosome assembly in response to DNA repair failure," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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