title: The role of the human psoralen 4 (hPso4) protein complex in replication stress and homologous recombination.
abstract: Psoralen 4 (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 interstrand 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 hydroxyurea-induced DNA double strand breaks (DSBs), and increased sensitivity to a poly(ADP-ribose) polymerase inhibitor. Furthermore, we show that hPso4 is involved in the repair of DSBs by homologous recombination, probably by regulating the BRCA1 protein levels and the generation of single strand DNA at DSBs. Together, our results demonstrate that hPso4 participates in cell proliferation and the maintenance of genome stability by regulating homologous recombination. The involvement of hPso4 in the recombinational repair of DSBs provides an explanation for the sensitivity of Pso4-deficient cells to DNA interstrand cross-links.
authors.affiliation: From the Division of Hematology-Oncology, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131 and.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abbas
authors.affiliation: From the Division of Hematology-Oncology, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131 and.
authors.forename: Ilanchezhian
authors.initials: I
authors.lastname: Shanmugam
authors.affiliation: From the Division of Hematology-Oncology, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131 and.
authors.forename: Manal
authors.initials: M
authors.lastname: Bsaili
authors.affiliation: the Department of Medicine, University of Florida, Gainesville, Florida 32611.
authors.forename: Robert
authors.initials: R
authors.lastname: Hromas
authors.affiliation: From the Division of Hematology-Oncology, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131 and moshaheen@salud.unm.edu.
authors.forename: Monte
authors.initials: M
authors.lastname: Shaheen
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D045643:DNA Repair Enzymes / Q000172:deficiency / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000096:biosynthesis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D059765:Homologous Recombination / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D000072260:RNA Splicing Factors
chemical_list: D019313:BRCA1 Protein; D004277:DNA, Single-Stranded; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D000072260:RNA Splicing Factors; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human; D006918:Hydroxyurea
keywords: BRCA1; DNA Damage; DNA Repair; DNA Replication; Homologous Recombination