ATAD5 functions as a regulatory platform for Ub-PCNA deubiquitination.
Eunjin Ryu1,2, Juyeong Yoo1,2, Mi-Sun Kang1
1Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
Summary
ATAD5 acts as a scaffold to recruit deubiquitinases, enabling the removal of ubiquitin from proliferating cell nuclear antigen (PCNA). This process is essential for safely deactivating DNA repair pathways after DNA damage.
Area of Science:
- Molecular Biology
- DNA Repair Mechanisms
- Ubiquitin-Proteasome System
Background:
- Proliferating cell nuclear antigen (PCNA) ubiquitination is vital for DNA lesion bypass.
- The mechanism of PCNA deubiquitination after DNA fork stalling resolution is not well understood.
Purpose of the Study:
- To elucidate the mechanism of PCNA deubiquitination.
- To identify the factors involved in removing ubiquitin from PCNA.
Main Methods:
- Investigated the role of ATAD5 in PCNA deubiquitination.
- Utilized biochemical assays to study protein-protein interactions and deubiquitination activity.
- Analyzed ATAD5 mutants for sensitivity to DNA-damaging agents.
Main Results:
- The N-terminal domain of ATAD5 (ATAD5-N) functions as a scaffold for Ub-PCNA deubiquitination.
- ATAD5 recognizes DNA-loaded Ub-PCNA via specific DNA-binding and PCNA-binding motifs.
- ATAD5 forms a complex with UAF1-USP1 and enhances deubiquitination by USP7 and USP11.
- ATAD5 mutants lacking UAF1-binding show increased sensitivity to DNA-damaging agents.
Conclusions:
- ATAD5 and USP deubiquitinases cooperate to remove ubiquitin from PCNA.
- This coordinated action is critical for PCNA release from DNA and safe deactivation of DNA repair.
- ATAD5 is a key regulator in the PCNA deubiquitination pathway.
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