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• W2040278857 endingPage "239" @default.
• W2040278857 startingPage "229" @default.
• W2040278857 abstract "Transformation of cells by the human T cell leukemia virus type 1 occurs via mechanisms unique among oncogenic retroviruses. A prevailing hypothesis for HTLV-1-mediated cellular transformation is that expression of the viral transactivator, Tax, induces genomic instability. Tax-mediated failure in the cellular repair response is one possible mechanism for loss in genomic integrity. Here we have examined the in vivo repair response of Tax-expressing cells to determine the underlying defects that contribute to loss of genomic integrity. In these studies we examined the effects of de novo Tax-expression in naive pre-neoplastic REF52 cells. DNA-damage-induced p53 stabilization and concomitant transient stabilization of p21 were clearly evident in Tax-expressing cells. Likewise, the damage-induced apoptotic response of Tax-expressing cells was normal. However, the damage-induced G1 checkpoint was abrogated in either p53+ or p53- cellular backgrounds. Although nucleotide excision repair (NER) of asynchronous Tax-expressing cells was impaired, cell-cycle-independent assessment of NER in the global excision repair assay demonstrated comparable NER activity in Tax-expressing cells, suggesting that the failure of G1 checkpoint contributes to NER deficiency. Interestingly, we observed a dramatic increase in apoptosis and UV sensitivity of Tax-expressing p53-/- cells when compared to Tax-expressing p53+/+ cells. These data demonstrate that Tax-mediated cellular genomic instability arises from attenuation of cell-cycle checkpoint and imply a clonal dependence on p53 status separate from genomic integrity." @default.
• W2040278857 created "2016-06-24" @default.
• W2040278857 creator A5025982554 @default.
• W2040278857 creator A5066466430 @default.
• W2040278857 date "2003-01-01" @default.
• W2040278857 modified "2023-10-18" @default.
• W2040278857 title "The HTLV-1 Tax Oncoprotein Attenuates DNA Damage Induced G1 Arrest and Enhances Apoptosis in p53 Null Cells" @default.
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• W2040278857 doi "https://doi.org/10.1006/viro.2002.1642" @default.
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• W2040278857 hasPublicationYear "2003" @default.
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