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ATAD5-BAZ1B interaction modulates PCNA ubiquitination during DNA repair

Author

Listed:
  • Yeongjae Kim

    (Institute for Basic Science
    Ulsan National Institute of Science and Technology)

  • Na Young Ha

    (Institute for Basic Science)

  • Mi-Sun Kang

    (Institute for Basic Science)

  • Eunjin Ryu

    (Institute for Basic Science
    Harvard Medical School)

  • Geunil Yi

    (Institute for Basic Science
    Ulsan National Institute of Science and Technology)

  • Juyeong Yoo

    (Institute for Basic Science
    Ulsan National Institute of Science and Technology)

  • Nalae Kang

    (Institute for Basic Science)

  • Byung-Gyu Kim

    (Institute for Basic Science)

  • Kyungjae Myung

    (Institute for Basic Science
    Ulsan National Institute of Science and Technology)

  • Sukhyun Kang

    (Institute for Basic Science)

Abstract

Mono-ubiquitinated PCNA (mono-Ub-PCNA) is generated when replication forks encounter obstacles, enabling the bypass of DNA lesions. After resolving stalled forks, Ub-PCNA must be de-ubiquitinated to resume high-fidelity DNA synthesis. ATAD5, in cooperation with the UAF1-USP1 complex, is responsible for this de-ubiquitination. However, the precise regulation of timely Ub-PCNA de-ubiquitination remains unclear. Our research reveals that BAZ1B, a regulatory subunit of the BAZ1B-SMARCA5 chromatin-remodeling complex (also known as the WICH complex), plays a crucial role in fine-tuning the de-ubiquitination process of Ub-PCNA. The BAZ1B binding region of ATAD5 encompasses the UAF1-binding domain of ATAD5. Disruption of the ATAD5-BAZ1B interaction results in premature de-ubiquitination of Ub-PCNA following treatment with hydrogen peroxide. Cells with impaired BAZ1B binding to ATAD5 display increased sensitivity to oxidative stress compared to wild-type cells. These findings suggest that BAZ1B prevents premature Ub-PCNA de-ubiquitination, thereby safeguarding genome integrity.

Suggested Citation

  • Yeongjae Kim & Na Young Ha & Mi-Sun Kang & Eunjin Ryu & Geunil Yi & Juyeong Yoo & Nalae Kang & Byung-Gyu Kim & Kyungjae Myung & Sukhyun Kang, 2024. "ATAD5-BAZ1B interaction modulates PCNA ubiquitination during DNA repair," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55005-3
    DOI: 10.1038/s41467-024-55005-3
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