This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Linke, S. P. Articles by Harris, C. C. Search for Related Content PubMed PubMed Citation Articles by Linke, S. P. Articles by Harris, C. C.

p53 Interacts with hRAD51 and hRAD54, and Directly Modulates Homologous Recombination^{1 ,2}

Laboratories of Human Carcinogenesis [S. P. L., S. S., N. K., B. A. J., R. P., X. W. W., L. J. H., Q. Y., C. C. H.] and Experimental Carcinogenesis [S. H. G.], National Cancer Institute, NIH, Bethesda, Maryland 20892, and Institute of Human Genetics, University of Luebeck, Lübeck, Germany D-23538 [S. B., S. M., W. H., H-W. S.]

p53 inhibits tumorigenesis through a variety of functions, including mediation of cell cycle arrest, premature senescence, and apoptosis.p53 also can associate with several DNA helicases and proteins involved in homologous recombination. In this study, we show that p53, hRAD51, and hRAD54 coimmunoprecipitated and colocalized with each other at endogenous levels in normal cells. Colocalization was observed with the phosphoserine-15 form of p53 at presumed DNA processing sites after the induction of DNA breaks. hRAD54 bound directly to the p53 COOH terminus in vitro without a nucleic acid intermediate. We then investigated the functional consequences of these protein interactions. A host cell reactivation assay revealed that the elevation in recombination observed after p53 inactivation is dependent on the hRAD51 pathway and that p53-dependent antirecombinogenic activity can be attributed to p53 binding to hRAD51 directly. These data support the hypothesis that p53 helps maintain genetic stability through transcription-independent modulation of homologous recombination factors.

This article has been cited by other articles:

				A. Restle, M. Farber, C. Baumann, M. Bohringer, K. H. Scheidtmann, C. Muller-Tidow, and L. Wiesmuller Dissecting the role of p53 phosphorylation in homologous recombination provides new clues for gain-of-function mutants Nucleic Acids Res., August 12, 2008; (2008) gkn503v1. [Abstract] [Full Text] [PDF]

				J.-Y. Park, H.-W. Yoo, B.-R. Kim, R. Park, S.-Y. Choi, and Y. Kim Identification of a novel human Rad51 variant that promotes DNA strand exchange Nucleic Acids Res., June 1, 2008; 36(10): 3226 - 3234. [Abstract] [Full Text] [PDF]

				G. Ambrosini, S. L. Seelman, L.-X. Qin, and G. K. Schwartz The Cyclin-Dependent Kinase Inhibitor Flavopiridol Potentiates the Effects of Topoisomerase I Poisons by Suppressing Rad51 Expression in a p53-Dependent Manner Cancer Res., April 1, 2008; 68(7): 2312 - 2320. [Abstract] [Full Text] [PDF]

				V. Tripathi, S. Kaur, and S. Sengupta Phosphorylation-dependent interactions of BLM and 53BP1 are required for their anti-recombinogenic roles during homologous recombination Carcinogenesis, January 1, 2008; 29(1): 52 - 61. [Abstract] [Full Text] [PDF]

				S. C. Short, C. Martindale, S. Bourne, G. Brand, M. Woodcock, and P. Johnston DNA repair after irradiation in glioma cells and normal human astrocytes Neuro-oncol, October 1, 2007; 9(4): 404 - 411. [Abstract] [Full Text] [PDF]

				A. Marusyk, L. J. Wheeler, C. K. Mathews, and J. DeGregori p53 Mediates Senescence-Like Arrest Induced by Chronic Replicational Stress Mol. Cell. Biol., August 1, 2007; 27(15): 5336 - 5351. [Abstract] [Full Text] [PDF]

				J. Lu, L.-E Wang, P. Xiong, E. M. Sturgis, M. R. Spitz, and Q. Wei 172G>T variant in the 5' untranslated region of DNA repair gene RAD51 reduces risk of squamous cell carcinoma of the head and neck and interacts with a P53 codon 72 variant Carcinogenesis, May 1, 2007; 28(5): 988 - 994. [Abstract] [Full Text] [PDF]

				J. A.F. Hannay, J. Liu, Q.-S. Zhu, S. V. Bolshakov, L. Li, P. W.T. Pisters, A. J.F. Lazar, D. Yu, R. E. Pollock, and D. Lev Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma cells: a role for p53/activator protein 2 transcriptional regulation Mol. Cancer Ther., May 1, 2007; 6(5): 1650 - 1660. [Abstract] [Full Text] [PDF]

				M. Enari, K. Ohmori, I. Kitabayashi, and Y. Taya Requirement of clathrin heavy chain for p53-mediated transcription Genes & Dev., May 1, 2006; 20(9): 1087 - 1099. [Abstract] [Full Text] [PDF]

				N. Levy, A. Martz, A. Bresson, C. Spenlehauer, G. de Murcia, and J. Menissier-de Murcia XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage Nucleic Acids Res., January 5, 2006; 34(1): 32 - 41. [Abstract] [Full Text] [PDF]

				D. Subramanian and J. D. Griffith p53 Monitors Replication Fork Regression by Binding to "Chickenfoot" Intermediates J. Biol. Chem., December 30, 2005; 280(52): 42568 - 42572. [Abstract] [Full Text] [PDF]

				J. Mercer, N. Figg, V. Stoneman, D. Braganza, and M. R. Bennett Endogenous p53 Protects Vascular Smooth Muscle Cells From Apoptosis and Reduces Atherosclerosis in ApoE Knockout Mice Circ. Res., April 1, 2005; 96(6): 667 - 674. [Abstract] [Full Text] [PDF]

				E. Schildkraut, C. A. Miller, and J. A. Nickoloff Gene conversion and deletion frequencies during double-strand break repair in human cells are controlled by the distance between direct repeats Nucleic Acids Res., March 14, 2005; 33(5): 1574 - 1580. [Abstract] [Full Text] [PDF]

				A. Friedler, D. B. Veprintsev, T. Rutherford, K. I. von Glos, and A. R. Fersht Binding of Rad51 and Other Peptide Sequences to a Promiscuous, Highly Electrostatic Binding Site in p53 J. Biol. Chem., March 4, 2005; 280(9): 8051 - 8059. [Abstract] [Full Text] [PDF]

				M. O. Trastoy, M. Defais, and F. Larminat Resistance to the antibiotic Zeocin by stable expression of the Sh ble gene does not fully suppress Zeocin-induced DNA cleavage in human cells Mutagenesis, March 1, 2005; 20(2): 111 - 114. [Abstract] [Full Text] [PDF]

				S. Yun, C. Lie-A-Cheong, and A. C. G. Porter Discriminatory suppression of homologous recombination by p53 Nucleic Acids Res., December 15, 2004; 32(22): 6479 - 6489. [Abstract] [Full Text] [PDF]

				J. P. Banath, S. H. MacPhail, and P. L. Olive Radiation Sensitivity, H2AX Phosphorylation, and Kinetics of Repair of DNA Strand Breaks in Irradiated Cervical Cancer Cell Lines Cancer Res., October 1, 2004; 64(19): 7144 - 7149. [Abstract] [Full Text] [PDF]

				S. Sengupta, A. I. Robles, S. P. Linke, N. I. Sinogeeva, R. Zhang, R. Pedeux, I. M. Ward, A. Celeste, A. Nussenzweig, J. Chen, et al. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest J. Cell Biol., September 13, 2004; 166(6): 801 - 813. [Abstract] [Full Text] [PDF]

				R. Del Carratore, A. Petrucci, M. Simili, G. Fronza, and A. Galli Involvement of human p53 in induced intrachromosomal recombination in Saccharomyces cerevisiae Mutagenesis, September 1, 2004; 19(5): 333 - 339. [Abstract] [Full Text] [PDF]

				F. d'Adda di Fagagna, S.-H. Teo, and S. P. Jackson Functional links between telomeres and proteins of the DNA-damage response Genes & Dev., August 1, 2004; 18(15): 1781 - 1799. [Abstract] [Full Text] [PDF]

				G. S. Boehden, A. Restle, R. Marschalek, C. Stocking, and L. Wiesmuller Recombination at chromosomal sequences involved in leukaemogenic rearrangements is differentially regulated by p53 Carcinogenesis, August 1, 2004; 25(8): 1305 - 1313. [Abstract] [Full Text] [PDF]

				T. Habu, N. Wakabayashi, K. Yoshida, K. Yomogida, Y. Nishimune, and T. Morita p53 protein interacts specifically with the meiosis-specific mammalian RecA-like protein DMC1 in meiosis Carcinogenesis, June 1, 2004; 25(6): 889 - 893. [Abstract] [Full Text] [PDF]