The HTLV-1 Tax oncoprotein represses Ku80 gene expression
| Autor: | Tajhal Dayaram, Susan J. Marriott, Razvan I. Ducu |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Gene Expression Regulation
Viral Ku80 DNA repair Tax Micronuclei Biology Article Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Transcription (biology) Virology Gene expression Humans DNA Breaks Double-Stranded RNA Messenger Promoter Regions Genetic Ku Autoantigen 030304 developmental biology Human T-lymphotropic virus 1 0303 health sciences Antigens Nuclear Gene Products tax DNA repair protein XRCC4 Molecular biology Double Strand Break Repair DNA-Binding Proteins Non-homologous end joining chemistry HTLV-1 030220 oncology & carcinogenesis DNA Viral RNA Viral DNA |
| Zdroj: | Virology. 416:1-8 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2011.04.012 |
| Popis: | The HTLV-I oncoprotein Tax interferes with DNA double strand break repair. Since non-homologous end joining (NHEJ) is a major pathway used to repair DNA double strand breaks we examined the effect of Tax on this pathway, with particular interest in the expression and function of Ku80, a critical component of the NHEJ pathway. Tax expression decreased Ku80 mRNA and protein levels, and repressed transcription from the Ku80 promoter. Conversely, Ku80 mRNA increased following siRNA knockdown of Tax in HTLV-I infected cells. Tax expression was associated with an elevated number of micronuclei and nucleoplasmic bridges, hallmarks of improper DNA double strand break repair. Our studies identified Tax as a transcriptional repressor of Ku80 that correlates with decreased DNA repair function. The reduction of Ku80 transcription by Tax may deplete the cell of an essential DNA break binding protein, resulting in reduced repair of DNA double strand breaks and accumulation genomic mutations. |
| Databáze: | OpenAIRE |
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