The PSO4 protein complex associates with replication protein A (RPA) and modulates the activation of ataxia telangiectasia-mutated and Rad3-related (ATR).
The PSO4 core complex is composed of PSO4/PRP19/SNEV, CDC5L, PLRG1, and BCAS2/SPF27. Besides its well defined functions in pre-mRNA splicing, the PSO4 complex has been shown recently to participate in the DNA damage response. However, the specific role for the PSO4 complex in the DNA damage response pathways is still not clear. Here we show that both the BCAS2 and PSO4 subunits of the PSO4 complex directly interact and colocalize with replication protein A (RPA). Depletion of BCAS2 or PSO4 impairs the recruitment of ATR-interacting protein (ATRIP) to DNA damage sites and compromises CHK1 activation and RPA2 phosphorylation. Moreover, we demonstrate that both the RPA1-binding ability of BCAS2 and the E3 ligase activity of PSO4 are required for efficient accumulation of ATRIP at DNA damage sites and the subsequent CHK1 activation and RPA2 phosphorylation. Our results suggest that the PSO4 complex functionally interacts with RPA and plays an important role in the DNA damage response.
Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Li
L
Wan
Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: jhuang@zju.edu.cn.
Jun
J
Huang
D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D004249:DNA Damage; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000072260:RNA Splicing Factors; D051716:Replication Protein A / Q000378:metabolism*
C120624:BCAS2 protein, human; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D051716:Replication Protein A; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human
Cell Biology; Checkpoint Control; DNA Damage Response; DNA Repair; Signal Transduction