title: Alternative end-joining pathway(s): bricolage at DNA breaks.
abstract: To cope with DNA double strand break (DSB) genotoxicity, cells have evolved two main repair pathways: homologous recombination which uses homologous DNA sequences as repair templates, and non-homologous Ku-dependent end-joining involving direct sealing of DSB ends by DNA ligase IV (Lig4). During the last two decades a third player most commonly named alternative end-joining (A-EJ) has emerged, which is defined as any Ku- or Lig4-independent end-joining process. A-EJ increasingly appears as a highly error-prone bricolage on DSBs and despite expanding exploration, it still escapes full characterization. In the present review, we discuss the mechanism and regulation of A-EJ as well as its biological relevance under physiological and pathological situations, with a particular emphasis on chromosomal instability and cancer. Whether or not it is a genuine DSB repair pathway, A-EJ is emerging as an important cellular process and understanding A-EJ will certainly be a major challenge for the coming years.
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), BP 64182, 205 route de Narbonne, 31077 Toulouse, Cedex4, France; Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France; Equipe labellisée Ligue Nationale Contre le Cancer, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Frit
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), BP 64182, 205 route de Narbonne, 31077 Toulouse, Cedex4, France; Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France; Equipe labellisée Ligue Nationale Contre le Cancer, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Barboule
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), BP 64182, 205 route de Narbonne, 31077 Toulouse, Cedex4, France; Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France; Equipe labellisée Ligue Nationale Contre le Cancer, France.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), BP 64182, 205 route de Narbonne, 31077 Toulouse, Cedex4, France; Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France; Equipe labellisée Ligue Nationale Contre le Cancer, France.
authors.forename: Dennis
authors.initials: D
authors.lastname: Gomez
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), BP 64182, 205 route de Narbonne, 31077 Toulouse, Cedex4, France; Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France; Equipe labellisée Ligue Nationale Contre le Cancer, France. Electronic address: calsou@ipbs.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Calsou
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism; D043171:Chromosomal Instability; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D011088:DNA Ligases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D011088:DNA Ligases; D045643:DNA Repair Enzymes
keywords: Class-switch recombination; DNA double-strand breaks (DSBs); DNA repair; Non-homologous endjoining (NHEJ); Telomere; V(D)J Recombination