title: Partial complementation of a DNA ligase I deficiency by DNA ligase III and its impact on cell survival and telomere stability in mammalian cells.
abstract: DNA ligase I (LigI) plays a central role in the joining of strand interruptions during replication and repair. In our current study, we provide evidence that DNA ligase III (LigIII) and XRCC1, which form a complex that functions in single-strand break repair, are required for the proliferation of mammalian LigI-depleted cells. We show from our data that in cells with either dysfunctional LigI activity or depleted of this enzyme, both LigIII and XRCC1 are retained on the chromatin and accumulate at replication foci. We also demonstrate that the LigI and LigIII proteins cooperate to inhibit sister chromatid exchanges but that only LigI prevents telomere sister fusions. Taken together, these results suggest that in cells with dysfunctional LigI, LigIII contributes to the ligation of replication intermediates but not to the prevention of telomeric instability.
authors.affiliation: Equipe Avenir, INSERM, 92265, Fontenay-aux-Roses, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Chalony
authors.forename: Françoise
authors.initials: F
authors.lastname: Hoffschir
authors.forename: Laurent R
authors.initials: LR
authors.lastname: Gauthier
authors.forename: Julia
authors.initials: J
authors.lastname: Gross
authors.forename: Denis S
authors.initials: DS
authors.lastname: Biard
authors.forename: François D
authors.initials: FD
authors.lastname: Boussin
authors.forename: Vincent
authors.initials: V
authors.lastname: Pennaneach
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics; D003114:Colony-Forming Units Assay; D004249:DNA Damage / Q000235:genetics; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000201:enzymology; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology; D005455:Fluorescent Antibody Technique; D005816:Genetic Complementation Test; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins; D034741:RNA, Small Interfering / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000235:genetics; D016615:Telomere / Q000737:chemistry* / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C000607892:LIG1 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D034741:RNA, Small Interfering; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D029867:Xenopus Proteins; C000619352:Xrcc1 protein, mouse; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human; C000618818:Lig3 protein, mouse