title: DNA repair endonuclease ERCC1-XPF as a novel therapeutic target to overcome chemoresistance in cancer therapy.
abstract: The ERCC1-XPF complex is a structure-specific endonuclease essential for the repair of DNA damage by the nucleotide excision repair pathway. It is also involved in other key cellular processes, including DNA interstrand crosslink (ICL) repair and DNA double-strand break (DSB) repair. New evidence has recently emerged, increasing our understanding of its requirement in these additional roles. In this review, we focus on the protein-protein and protein-DNA interactions made by the ERCC1 and XPF proteins and discuss how these coordinate ERCC1-XPF in its various roles. In a number of different cancers, high expression of ERCC1 has been linked to a poor response to platinum-based chemotherapy. We discuss prospects for the development of DNA repair inhibitors that target the activity, stability or protein interactions of the ERCC1-XPF complex as a novel therapeutic strategy to overcome chemoresistance.
authors.affiliation: MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Ewan M
authors.initials: EM
authors.lastname: McNeil
authors.forename: David W
authors.initials: DW
authors.lastname: Melton
mesh_terms: D004260:DNA Repair; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy*; D017434:Protein Structure, Tertiary; D059505:Telomere Homeostasis
chemical_list: D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; C071447:ERCC1 protein, human; D004720:Endonucleases