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Homologous recombination induced by replication inhibition, is stimulated by expression of mutant p53

Oncogene volume 21, pages 488–492 (2002)Cite this article

Abstract

Cell cycle control, faithful DNA replication, repair and recombination are associated in a network of pathways controlling genome maintenance. In mammalian cells, inhibition of replication produces DNA breaks and induces RAD51-dependent recombination, in a late step. Here we examine whether the status of p53 affects this process in mouse L-cells containing a recombination substrate. We show that expression of the mutant His175p53 strongly stimulates recombination induced by aphidicolin, in a late step (kinetically related to the RAD51 step). Mutant p53 stimulates recombination induced by the replication elongation inhibitors (aphidicolin, hydroxyurea and Ara-C) but is without effect on recombination induced by the initiation inhibitors (mimosine and ciclopirox olamine). We compared the impact of several p53 mutations showing different effects on the G1 checkpoint and on recombination. We show that the mutant Pro273p53 protein, which does not alter the G1 checkpoint, strongly stimulates recombination induced by elongation inhibitors. These results show that p53 can act on recombination induced by replication arrest independently of its role in the G1 checkpoint. An action of p53 via the RAD51 pathway is discussed.

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Acknowledgements

We thank D Rouillard (Institut Curie, Paris) for FACS expertise. We are grateful to Drs P Bertrand, D Marsh, R Monnat for critical reading of the manuscript. Thanks are due to M Liskay for providing the pJS3-10 cell lines. Y Saintigny was supported by a fellowship from ‘la Foundation pour la Recherche Médicale’. This work was supported by Electricité de France, ARC (9822 and 9238).

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  1. Département de Radiobiologie et Radiopathologie, UMR217 CNRS-CEA, CEA, Direction des Sciences du Vivant, 60-68 avenue du Général Leclerc, 92 265 Fontenay aux Roses, cedex, France

    Yannick Saintigny & Bernard S Lopez

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  1. Yannick Saintigny
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  2. Bernard S Lopez
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Correspondence to Bernard S Lopez.

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Saintigny, Y., Lopez, B. Homologous recombination induced by replication inhibition, is stimulated by expression of mutant p53. Oncogene 21, 488–492 (2002). https://doi.org/10.1038/sj.onc.1205040

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