Biochemistry Commons^™

Structure And Function Relationships Between Atpase Family, Aaa Domain Containing Protein 5, Proliferating Cell Nuclear Antigen, And Usp1-Associated Factor 1, Tam T. Bui

Electronic Thesis and Dissertation Repository

The genome is constantly damaged by intracellular and extracellular factors. At sites of DNA damage, replication forks are stalled, leading monoubiquitination of proliferating cell nuclear antigen (PCNA). Monoubiquitination of PCNA promote the switch from regular high-fidelity polymerases to Y-family polymerases for bypassing damaged DNA. Prolonged replication by these polymerases may lead to increased mutagenesis, so tight regulation of this process is required. ATAD5 recruits a deubiquitinase complex consisting of ubiquitin-specific protease 1 (USP1) and USP1-associated factor 1 (UAF1) to control PCNA monoubiquitination. The mechanism by which ATAD5 and PCNA interact has been previously unexplored. We show through biochemical and structural …