Article
- The EMBO Journal (2006) 25, 763 - 773
- doi:10.1038/sj.emboj.7600972
Published online: 2 February 2006
Subject Categories:
Activation of p38 MAP kinase by DNA double-strand breaks in V(D)J recombination induces a G2/M cell cycle checkpoint
Gustavo Pedraza-Alva1,2, Miroslav Koulnis1, Colette Charland1, Tina Thornton1, James L Clements3, Mark S Schlissel4 and Mercedes Rincón1
- Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT, USA
- Instituto de Biotecnología, Universidad Nacional Autónoma de México. Cuernavaca, Mor., México
- Department of Immunology, Cancer Cell Center, Roswell Park Cancer Institute, Buffalo, NY, USA
- Department of Molecular & Cell Biology, University of California-Berkeley, Berkeley, CA, USA
Correspondence to:
Mercedes Rincón, Department of Medicine/Immunobiology Program, Given Medical Building D-305, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405, USA. Tel.: +1 802 656 0937; Fax: +1 802 656 3854; E-mail: mrincon@zoo.uvm.edu
Received 23 September 2005; Accepted 2 January 2006
Abstract
Delay of cell cycle progression in response to double-strand DNA breaks (DSBs) is critical to allow time for DNA repair and prevent cellular transformation. Here, we show that the p38 mitogen-activated protein (MAP) kinase signaling pathway is activated in immature thymocytes along with TcR
gene V(D)J recombination. Active p38 MAP kinase promotes a G2/M cell cycle checkpoint through the phosphorylation and activation of p53 in these cells in vivo. Inactivation of p38 MAP kinase and p53 is required for DN3 thymocytes to exit the G2/M checkpoint, progress through mitosis and further differentiate. We propose that p38 MAP kinase is activated by V(D)J-mediated DSBs and induces a p53-mediated G2/M checkpoint to allow DNA repair and prevent cellular transformation.
Keywords:
- G2/M checkpoint,
- p38 MAP kinase,
- p53,
- thymocyte development,
- V(D)J recombination
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