{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Roshan P"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)","U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)"],"pagination":["92"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12770403"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(1)"],"pubmed_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"],"journal":["Nature communications"],"pubmed_title":["Mechanism of RPA phosphocode priming and tuning by CDK1/WEE1 signaling circuit."],"pmcid":["PMC12770403"],"funding_grant_id":["R35GM149320","S10OD030343","R01GM143179"],"pubmed_authors":["Vayyeti A","Luebbers R","Kaushik V","Antony E","Roshan P","Mistry A","Deveryshetty J","Origanti S","Antony A"],"additional_accession":[]},"is_claimable":false,"name":"Mechanism of RPA phosphocode priming and tuning by CDK1/WEE1 signaling circuit.","description":"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","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-06T10:55:25.245Z","creation":"2026-05-29T03:12:48.876Z"},"accession":"S-EPMC12770403","cross_references":{"pubmed":["41365883"],"doi":["10.1038/s41467-025-66794-6"]}}