title: Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair.
abstract: One of the major DNA interstrand cross-link (ICL) repair pathways in mammalian cells is coupled to replication, but the mechanistic roles of the critical factors involved remain largely elusive. Here, we show that purified human SNM1A (hSNM1A), which exhibits a 5'-3' exonuclease activity, can load from a single DNA nick and digest past an ICL on its substrate strand. hSNM1A-depleted cells are ICL-sensitive and accumulate replication-associated DNA double-strand breaks (DSBs), akin to ERCC1-depleted cells. These DSBs are Mus81-induced, indicating that replication fork cleavage by Mus81 results from the failure of the hSNM1A- and XPF-ERCC1-dependent ICL repair pathway. Our results reveal how collaboration between hSNM1A and XPF-ERCC1 is necessary to initiate ICL repair in replicating human cells.
authors: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.
authors: Anderson T
authors: AT
authors: Wang
authors: Blanka
authors: B
authors: Sengerová
authors: Emma
authors: E
authors: Cattell
authors: Takabumi
authors: T
authors: Inagawa
authors: Janet M
authors: JM
authors: Hartley
authors: Konstantinos
authors: K
authors: Kiakos
authors: Nicola A
authors: NA
authors: Burgess-Brown
authors: Lonnie P
authors: LP
authors: Swift
authors: Jacqueline H
authors: JH
authors: Enzlin
authors: Christopher J
authors: CJ
authors: Schofield
authors: Opher
authors: O
authors: Gileadi
authors: John A
authors: JA
authors: Hartley
authors: Peter J
authors: PJ
authors: McHugh
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C095888:xeroderma pigmentosum group F protein; D004247:DNA; C493741:DCLRE1B protein, human; C071447:ERCC1 protein, human; D004720:Endonucleases; D005090:Exodeoxyribonucleases; C498772:MUS81 protein, human; D045643:DNA Repair Enzymes