WDR48
Description
The WDR48 (WD repeat domain 48) is a protein-coding gene located on chromosome 3.
WDR48, also known as UAF1 (USP1-associated factor 1), is a protein that plays a critical role in regulating the activity of deubiquitinating enzymes (DUBs), particularly USP1, USP12, and USP46. It enhances the deubiquitination of FANCD2 by USP1, acting as a strong activator of this process. WDR48 enhances the catalytic activity of DUBs without affecting their affinity for substrates, suggesting it modulates the rate of deubiquitination. It also promotes the activity of complexes containing USP12, leading to the stabilization of PHLPP1, a protein involved in tumor suppression. WDR48 interacts with USP12 and induces structural changes that activate the enzyme. Additionally, WDR48 collaborates with RAD51AP1 to facilitate DNA repair by stimulating RAD51-mediated homologous recombination. This process involves WDR48 binding to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), a function that is crucial for both USP1-mediated FANCD2 deubiquitination and RAD51-mediated recombination. WDR48 and RAD51AP1 work together to bind DNA during these processes. WDR48, in conjunction with ATAD5, participates in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA. Furthermore, it assists ATAD5 in recruiting RAD51 to stalled replication forks during replication stress. {ECO:0000269|PubMed:18082604, ECO:0000269|PubMed:19075014, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:24145035, ECO:0000269|PubMed:26388029, ECO:0000269|PubMed:27239033, ECO:0000269|PubMed:27373336, ECO:0000269|PubMed:27463890, ECO:0000269|PubMed:27650958, ECO:0000269|PubMed:31253762, ECO:0000269|PubMed:31844045, ECO:0000269|PubMed:32350107}
WDR48 is also known as Bun62, P80, SPG60, UAF1.
