title: The HTLV-1 Tax oncoprotein represses Ku80 gene expression.
abstract: 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.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. rducu@chpnet.org
authors.forename: Razvan I
authors.initials: RI
authors.lastname: Ducu
authors.forename: Tajhal
authors.initials: T
authors.lastname: Dayaram
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Marriott
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004279:DNA, Viral / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D012333:RNA, Messenger; D012367:RNA, Viral; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen