Mechanism of RPA phosphocode priming and tuning by CDK1/WEE1 signaling circuit.

ABSTRACT: Replication protein A (RPA) is a heterotrimeric single-strand DNA binding protein essential for DNA metabolism. Segregation of RPA functions in response to DNA damage is fine-tuned by hyperphosphorylation of the RPA32 subunit that is dependent on cyclin-dependent kinase (CDK)-mediated priming phosphorylation at the Ser-23 and Ser-29 sites. However, the mechanism of priming-driven hyperphosphorylation of RPA and the modulation of cell cycle progression by the RPA-CDK axis remains unresolved. Here, we uncover that the RPA70 subunit is also phosphorylated by CDK1 at Thr-191. This modification is crucial for G2 to M phase transition. This function is enacted through reciprocal regulation of CDK1 activity via a feedback circuit espoused by stabilization of WEE1 kinase. The Thr-191 phosphosite o

SUBMITTER: Roshan P 

PROVIDER: S-EPMC12770403 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature