title: DNA ligases I and III cooperate in alternative non-homologous end-joining in vertebrates.
abstract: Biochemical and genetic studies suggest that vertebrates remove double-strand breaks (DSBs) from their genomes predominantly by two non-homologous end joining (NHEJ) pathways. While canonical NHEJ depends on the well characterized activities of DNA-dependent protein kinase (DNA-PK) and LIG4/XRCC4/XLF complexes, the activities and the mechanisms of the alternative, backup NHEJ are less well characterized. Notably, the contribution of LIG1 to alternative NHEJ remains conjectural and although biochemical, cytogenetic and genetic experiments implicate LIG3, this contribution has not been formally demonstrated. Here, we take advantage of the powerful genetics of the DT40 chicken B-cell system to delineate the roles of LIG1 and LIG3 in alternative NHEJ. Our results expand the functions of LIG1 to alternative NHEJ and demonstrate a remarkable ability for LIG3 to backup DSB repair by NHEJ in addition to its essential function in the mitochondria. Together with results on DNA replication, these observations uncover a remarkable and previously unappreciated functional flexibility and interchangeability between LIG1 and LIG3.
authors.affiliation: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Paul
authors.forename: Minli
authors.initials: M
authors.lastname: Wang
authors.forename: Emil
authors.initials: E
authors.lastname: Mladenov
authors.forename: Alena
authors.initials: A
authors.lastname: Bencsik-Theilen
authors.forename: Theresa
authors.initials: T
authors.lastname: Bednar
authors.forename: Wenqi
authors.initials: W
authors.lastname: Wu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arakawa
authors.forename: George
authors.initials: G
authors.lastname: Iliakis
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D009154:Mutation; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus
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