title: Replication-mediated disassociation of replication protein A-XPA complex upon DNA damage: implications for RPA handing off.
abstract: RPA (replication protein A), the eukaryotic ssDNA (single-stranded DNA)-binding protein, participates in most cellular processes in response to genotoxic insults, such as NER (nucleotide excision repair), DNA, DSB (double-strand break) repair and activation of cell cycle checkpoint signalling. RPA interacts with XPA (xeroderma pigmentosum A) and functions in early stage of NER. We have shown that in cells the RPA-XPA complex disassociated upon exposure of cells to high dose of UV irradiation. The dissociation required replication stress and was partially attributed to tRPA hyperphosphorylation. Treatment of cells with CPT (camptothecin) and HU (hydroxyurea), which cause DSB DNA damage and replication fork collapse respectively and also leads to the disruption of RPA-XPA complex. Purified RPA and XPA were unable to form complex in vitro in the presence of ssDNA. We propose that the competition-based RPA switch among different DNA metabolic pathways regulates the dissociation of RPA with XPA in cells after DNA damage. The biological significances of RPA-XPA complex disruption in relation with checkpoint activation, DSB repair and RPA hyperphosphorylation are discussed.
authors.affiliation: Faculty of Preventive Medicine, Medical College, Wuhan University of Science and Technology, Wuhan, Hubei 430065, People’s Republic of China.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Jiang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zou
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
mesh_terms: D002166:Camptothecin / Q000494:pharmacology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004260:DNA Repair; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D051716:Replication Protein A / Q000032:analysis / Q000378:metabolism*; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000032:analysis / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; D051716:Replication Protein A; D051760:Xeroderma Pigmentosum Group A Protein; D004247:DNA; D006918:Hydroxyurea; D002166:Camptothecin