Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 10, Pages 6619-6626Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.543439
Keywords
Cell Biology; Checkpoint Control; DNA Damage Response; DNA Repair; Signal Transduction
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Funding
- National Program for Special Support of Eminent Professionals
- National Basic Research Program of China [2012CB944402, 2013CB911003]
- National Natural Science Funds for Distinguished Young Scholars
- Zhejiang University K.P. Chao's High Technology Development Foundation
- China Fundamental Research Funds for the Central Universities
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Background: The function of the PSO4 complex in response to DNA damage remains unclear. Results: The PSO4 complex is required for efficient accumulation of ATRIP at DNA damage sites and the subsequent CHK1 activation and RPA2 phosphorylation. Conclusion: The PSO4 complex modulates ATR activation through interaction with RPA. Significance: We reveal a role for RNA processing factor PSO4 in ATR activation. 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.
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