The PSO4 Complex Associates with RPA and Modulates the Activation of ATR [Signal Transduction]

January 17th, 2014 by Wan, L., Huang, J.

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 recently shown 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 BCAS2 and PSO4 subunits of the PSO4 complex directly interact and co-localize with RPA. Depletion of BCAS2 or PSO4 impairs the recruitment of 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.