Journal of Biological Chemistry
Volume 275, Issue 46, 17 November 2000, Pages 35926-35931
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DNA: REPLICATION REPAIR AND RECOMBINATION
Suppression of DNA Repair by Human T Cell Leukemia Virus Type 1 Tax Is Rescued by a Functional p53 Signaling Pathway*

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The Tax protein of human T cell leukemia virus type 1 is a viral transactivator and transforming protein. Tax is known to suppress cellular nucleotide excision repair (NER), and this activity has been proposed to play an important role in Tax transformation. In this study we have investigated the mechanism by which Tax suppresses NER with specific focus on the previously characterized ability of Tax to inhibit p53 function. Suppression of NER by Tax was rescued by overexpression of wild-type p53; however, a p53 transactivation-incompetent mutant did not restore NER activity. The cyclin-dependent kinase inhibitor p21, a major transcriptional target of p53, plays an important role in regulating DNA replication and repair. Overexpression of p21 reversed Tax-induced suppression of NER; however, a p21 C-terminal mutant that lacks the proliferating cell nuclear antigen binding domain did not restore NER activity. Thus, p53 and its downstream effector p21 can inhibit Tax-mediated suppression of DNA repair. These results imply that the inactivation of p53 function by Tax contributes to Tax suppression of DNA repair.

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Published, JBC Papers in Press, August 7, 2000, DOI 10.1074/jbc.M004397200

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This work was supported by NCI Grant CA-77371 from the National Institutes of Health (to S. J. M.). F. J. L. was supported in part by National Institutes of Health training grant (CA-09197) in Viral Oncology.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence and reprint requests should be addressed: Dept. of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Tel.: 713-798-4440; Fax: 713-798-3490; E-mail: [email protected].