The role of the human Psoralen 4 (hPso4) complex in replication stress and homologous recombination. [Cell Biology]

March 26th, 2014 by Abbas, M., Shanmugam, I., Bsaili, M., Hromas, R., Shaheen, M.

Pso4 is an evolutionarily conserved protein that has been implicated in a variety of cellular processes including RNA splicing and resistance to agents that cause DNA inter-strand cross-links. Here we show that the hPso4 complex is required for timely progression through S phase and transition through the G2/M checkpoint, and it functions in the repair of DNA lesions that arise during replication. Notably, hPso4 depletion results in delayed resumption of DNA replication after hydroxyurea -induced stalling of replication forks, reduced repair of spontaneous and HU-induced DNA double strand breaks, and increased sensitivity to a Poly (ADP-ribose) polymerase (PARP) inhibitor. Furthermore, we show that hPso4 is involved in the repair of DSBs repair by homologous recombination probably by regulating the BRCA1 protein levels and the generation of single-strand DNA (ssDNA) at DSBs. Together, our results demonstrate that hPso4 participates in cell proliferation and the maintenance of genome stability by regulating HR. The involvement of hPso4 in the recombinational repair of DSBs provides an explanation for the sensitivity of Pso4-deficient cells to DNA inter-strand cross-links.