Document Detail

XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells.
MedLine Citation:
PMID:  17057732     Owner:  NLM     Status:  MEDLINE    
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.
Y Saintigny; F Delacôte; D Boucher; D Averbeck; B S Lopez
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-23
Journal Detail:
Title:  Oncogene     Volume:  26     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-26     Completed Date:  2007-05-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  2769-80     Citation Subset:  IM    
UMR CNRS 217, CEA, Fontenay aux Roses Cédex, France.
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MeSH Terms
Cells, Cultured / radiation effects
DNA Breaks, Double-Stranded*
DNA-Binding Proteins / genetics,  physiology*
G1 Phase / genetics*,  radiation effects
G2 Phase / genetics*,  radiation effects
Gene Targeting
Infrared Rays
Mice, Knockout
Rad51 Recombinase / metabolism
Recombination, Genetic*
S Phase / genetics*,  radiation effects
Reg. No./Substance:
0/DNA-Binding Proteins; 0/XRCC4 protein, mouse; EC 2.7.7.-/Rad51 Recombinase

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