ATAD5-BAZ1B interaction modulates PCNA ubiquitination during DNA repair.

Area of Science:

• Molecular Biology
• DNA Replication and Repair
• Chromatin Remodeling

Background:

• Mono-ubiquitinated PCNA (mono-Ub-PCNA) is crucial for bypassing DNA lesions during replication stress.
• De-ubiquitination of PCNA is essential for resuming high-fidelity DNA synthesis after stalled fork resolution.
• The ATAD5-UAF1-USP1 complex mediates PCNA de-ubiquitination, but its regulation is not fully understood.

Purpose of the Study:

• To investigate the regulatory mechanisms controlling timely mono-Ub-PCNA de-ubiquitination.
• To elucidate the role of BAZ1B in the ATAD5-mediated de-ubiquitination pathway.
• To understand how BAZ1B influences cellular response to oxidative stress.

Main Methods:

• Investigated the interaction between BAZ1B and ATAD5, focusing on the ATAD5 UAF1-binding domain.
• Assessed the effect of disrupting the ATAD5-BAZ1B interaction on mono-Ub-PCNA levels after hydrogen peroxide treatment.
• Evaluated the sensitivity of cells with impaired BAZ1B binding to oxidative stress.

Main Results:

• BAZ1B, a subunit of the WICH complex, directly interacts with ATAD5 at its UAF1-binding domain.
• Disruption of the ATAD5-BAZ1B interaction leads to premature de-ubiquitination of mono-Ub-PCNA.
• Cells with impaired BAZ1B binding exhibit increased sensitivity to oxidative stress.

Conclusions:

• BAZ1B acts as a crucial regulator, preventing the premature de-ubiquitination of mono-Ub-PCNA.
• The BAZ1B-ATAD5 interaction is vital for maintaining genome integrity under oxidative stress conditions.
• BAZ1B fine-tunes the ATAD5-mediated de-ubiquitination process, ensuring proper DNA repair and cell survival.