Phosphorylation of RPA2 Is Required For TopBP1 Recruitment and ATR Activation

• DOI: 10.1096/fasebj.24.1_supplement.875.2
• Publication Date: 2021-06-15T18:26:36Z
• Authors: Shengqin Liu; Jason Glanzer; Greg Oakley
• Keywords: Replication protein A

Replication protein A (RPA) is a heterotrimer, single strand DNA binding involved in multiple aspects of metabolism. The N‐terminus the RPA2 subunit phosphorylated at sites during cell cycle progression and response to damage. To understand role phosphorylation, we generated stable lines expressing wild‐type mutant forms RPA with down regulation endogenous by shRNA. inability phosphorylate Ser4 Ser8 resulted loss phosphorylation Ser12 Thr21, but not Ser33 etoposide treatment. Cells showed defective G2/M checkpoint failed halt mitotic entry after Decreased Chk1 Mre11, suggested ATR activation was compromised cells RPA2. TopBP1, key activator ATR, recruited lesions Rad9. Rad9 also interacts through RPA1. Defective increased interaction inhibited decrease correlated TopBP1 recruitment chromatin Taken together, these results suggest that may regulate function altering its other proteins damage pathway.