Liu, S.; Byrne, B.M.; Byrne, T.N.; Oakley, G.G. Role of RPA Phosphorylation in the ATR-Dependent G2 Cell Cycle Checkpoint. Genes2023, 14, 2205.
Liu, S.; Byrne, B.M.; Byrne, T.N.; Oakley, G.G. Role of RPA Phosphorylation in the ATR-Dependent G2 Cell Cycle Checkpoint. Genes 2023, 14, 2205.
Liu, S.; Byrne, B.M.; Byrne, T.N.; Oakley, G.G. Role of RPA Phosphorylation in the ATR-Dependent G2 Cell Cycle Checkpoint. Genes2023, 14, 2205.
Liu, S.; Byrne, B.M.; Byrne, T.N.; Oakley, G.G. Role of RPA Phosphorylation in the ATR-Dependent G2 Cell Cycle Checkpoint. Genes 2023, 14, 2205.
Abstract
Cells respond to DNA double-strand breaks by initiating DSB repair and ensuing a cell cycle checkpoint. The primary responder to DSB repair is non-homologous end joining, an error prone repair pathway. However, when DSBs are generated after DNA replication in the G2 phase of the cell cycle, a second DSB repair pathway, homologous recombination, can come into action. Both ATM and ATR are important for DSB-induced DSB repair and checkpoint responses. One method of ATM and ATR working together is through the DNA end-resection of DSBs. As a readout and marker of DNA end-resection, RPA is phosphorylated at Ser4/Ser8 of the N-terminus of RPA32 in response to DSBs. Here, the significance of RPA32 Ser4/Ser8 phosphorylation in response to DNA damage, specifically in S phase to G2 phase of the cell cycle is examined. RPA32 Ser4/Ser8 phosphorylation in G2 synchronized cells is necessary for increases in TopBP1 and Rad9 accumulation on chromatin and full activation of the ATR-dependent G2 checkpoint. In addition, our data suggest RPA Ser4/Ser8 phosphorylation modulates ATM-dependent KAP-1 phosphorylation and Rad51 chromatin loading in G2 cells.
Keywords
DNA replication; DNA damage; cell cycle checkpoints
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
