title: Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice.
abstract: DNA double strand breaks are the most cytotoxic lesions that can occur on the DNA. They can be repaired by different mechanisms and optimal survival requires a tight control between them. Here we uncover protein deneddylation as a major controller of repair pathway choice. Neddylation inhibition changes the normal repair profile toward an increase on homologous recombination. Indeed, RNF111/UBE2M-mediated neddylation acts as an inhibitor of BRCA1 and CtIP-mediated DNA end resection, a key process in repair pathway choice. By controlling the length of ssDNA produced during DNA resection, protein neddylation not only affects the choice between NHEJ and homologous recombination but also controls the balance between different recombination subpathways. Thus, protein neddylation status has a great impact in the way cells respond to DNA breaks.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), 41092 Sevilla, Spain Departamento de Genética, Universidad de Sevilla, 41080 Sevilla, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jimeno
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), 41092 Sevilla, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Fernández-Ávila
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), 41092 Sevilla, Spain Departamento de Genética, Universidad de Sevilla, 41080 Sevilla, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Cruz-García
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), 41092 Sevilla, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cepeda-García
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), 41092 Sevilla, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gómez-Cabello
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), 41092 Sevilla, Spain Departamento de Genética, Universidad de Sevilla, 41080 Sevilla, Spain pablo.huertas@cabimer.es.
authors.forename: Pablo
authors.initials: P
authors.lastname: Huertas
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004260:DNA Repair; D004706:Endodeoxyribonucleases; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D059767:Recombinational DNA Repair; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; D002352:Carrier Proteins; D009687:Nuclear Proteins; D014452:Ubiquitins; D004247:DNA; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human