title: XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells.
abstract: Non-homologous end joining (NHEJ) and homologous recombination (HR) are two pathways that can compete or cooperate for DNA double-strand break (DSB) repair. NHEJ was previously shown to act throughout the cell cycle whereas HR is restricted to late S/G2. Paradoxically, we show here that defect in XRCC4 (NHEJ) leads to over-stimulation of HR when cells were irradiated in G1, not in G2. However, XRCC4 defect did not modify the strict cell cycle regulation for HR (i.e. in S/G2) as attested by (i) the formation of Rad51 foci in late S/G2 whatever the XRCC4 status, and (ii) the fact that neither Rad51 foci nor HR (gene conversion plus single-strand annealing) events induced by ionizing radiation were detected when cells were maintained blocked in G1. Finally, both gamma-H2AX analysis and pulse field gel electrophoresis showed that following irradiation in G1, some DSBs reached S/G2 in NHEJ-defective cells. Taken together, our results show that when cells are defective in G1/S arrest, DSB produced in G1 and left unrepaired by XRCC4 can be processed by HR but in late S/G2.
authors.affiliation: UMR CNRS 217, CEA, Fontenay aux Roses Cédex, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Saintigny
authors.forename: F
authors.initials: F
authors.lastname: Delacôte
authors.forename: D
authors.initials: D
authors.lastname: Boucher
authors.forename: D
authors.initials: D
authors.lastname: Averbeck
authors.forename: B S
authors.initials: BS
authors.lastname: Lopez
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016193:G1 Phase / Q000235:genetics* / Q000528:radiation effects; D016195:G2 Phase / Q000235:genetics* / Q000528:radiation effects; D018390:Gene Targeting; D007259:Infrared Rays; D051379:Mice; D018345:Mice, Knockout; D051135:Rad51 Recombinase / Q000378:metabolism; D011995:Recombination, Genetic; D016196:S Phase / Q000235:genetics* / Q000528:radiation effects
chemical_list: D004268:DNA-Binding Proteins; C511788:XRCC4 protein, mouse; D051135:Rad51 Recombinase