Proteomics

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ATAD5-BAZ1B interaction modulates PCNA ubiquitination during DNA repair


ABSTRACT: Mono-ubiquitinated PCNA (mono-Ub-PCNA) is generated when replication forks stall and facilitates the DNA lesion bypass process. After resolving a replication stall, Ub-PCNA needs to be de-ubiquitinated to resume high-fidelity DNA synthesis. ATAD5 cooperates with UAF1-USP1 to de-ubiquitinate mono-Ub-PCNA. However, it remains unclear how Ub-PCNA de-ubiquitination is regulated in a timely manner. We found that BAZ1B, a regulatory subunit of the chromatin-remodeling complex, fine-tunes de-ubiquitination of Ub-PCNA. The BAZ1B binding region of ATAD5 surrounds the ATAD5 UAF1-binding domain. Abrogation of the ATAD5-BAZ1B interaction leads to premature de-ubiquitination of Ub-PCNA after hydrogen peroxide treatment. BAZ1B-binding defective ATAD5 cells are more sensitive to oxidative stress compared to wild-type cells. These results suggest that BAZ1B inhibits premature Ub-PCNA de-ubiquitination to maintain genome integrity.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Byung-gyu kim  

LAB HEAD: Sukhyun Kang

PROVIDER: PXD050108 | Pride | 2025-05-06

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
1.raw Raw
1_2.raw Raw
2.raw Raw
20221125_MBS_IP_BAZ1B_S1_vs_S2.sf3 Other
20230214_MBS_ATAD5_S1_vs_S2.sf3 Other
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Publications

ATAD5-BAZ1B interaction modulates PCNA ubiquitination during DNA repair.

Kim Yeongjae Y   Ha Na Young NY   Kang Mi-Sun MS   Ryu Eunjin E   Yi Geunil G   Yoo Juyeong J   Kang Nalae N   Kim Byung-Gyu BG   Myung Kyungjae K   Kang Sukhyun S  

Nature communications 20241203 1


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-re  ...[more]

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