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XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells

Oncogene volume 26, pages 2769–2780 (2007)Cite this article

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 γ-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.

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Acknowledgements

We thank Dr Maria Jasin for providing XR-1 cells and I-SceI expression plasmid. We also thank Drs P Bertrand, F Lebrun and D Marsh for helpful discussion and critical reading of the paper. This work was supported by La Ligue Nationale contre le Cancer ‘Equipe labellisée, La Ligue 2005’.

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  1. Y Saintigny and F Delacôte: These authors contributed equally to this work

Authors and Affiliations

  1. UMR CNRS 217, CEA, Fontenay aux Roses, Cédex, France

    Y Saintigny, F Delacôte & B S Lopez

  2. UMR 2027 CNRS/Institut Curie, Section de recherche, Centre Universitaire Bât 110, Orsay, Cédex, France

    D Boucher & D Averbeck

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  1. Y Saintigny
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  2. F Delacôte
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  3. D Boucher
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Correspondence to B S Lopez.

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Saintigny, Y., Delacôte, F., Boucher, D. et al. XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells. Oncogene 26, 2769–2780 (2007). https://doi.org/10.1038/sj.onc.1210075

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