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

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 a€ects this process in mouse L-cells containing a recombination substrate. We show that expression of the mutant His175 p53 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 (aphidi-colin, hydroxyurea and Ara-C) but is without e€ect on recombination induced by the initiation inhibitors (mimosine and ciclopirox olamine). We compared the impact of several p53 mutations showing di€erent e€ects on the G1 checkpoint and on recombination. We show that the mutant Pro273 p53 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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Submitted on : Wednesday, November 28, 2018 - 2:50:23 PM
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Yannick Saintigny, Bernard Lopez. Homologous recombination induced by replication inhibition, is stimulated by expression of mutant p53. Oncogene, Nature Publishing Group, 2002, 21 (3), pp.488 - 492. ⟨10.1038/sj.onc.1205040⟩. ⟨cea-01938162⟩

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