The HIV-1 transactivator protein Tat is a potent inducer of the human DNA repair enzyme beta-polymerase.
OBJECTIVE: This study examines the effects of the HIV-1 regulatory proteins, Tat and Rev, on the expression of the DNA polymerase beta (beta-pol) gene, which encodes a key protein in the DNA base-excision repair pathway. The rationale for these experiments is to examine the potential involvement of base-excision repair protein deregulation in HIV-1-related lymphomas. DESIGN: Expression of beta-pol mRNA was examined in AIDS-related lymphomas and non-AIDS-related lymphomas and as a function of HIV-1 infection of B cells in culture. The effect of Tat or Rev over-expression on beta-pol promoter expression was tested by transient co-transfection assays with a beta-pol promoter reporter plasmid and a Tat or Rev over-expression plasmid. METHODS: Northern blot analysis was used to quantitate beta-pol expression in lymphoma and cells. Raji cells were co-transfected with a chloramphenicol acetyltransferase (CAT) reporter plasmid and a plasmid over-expressing Tat or Rev. CAT activity was measured in transfected cells. RESULTS: beta-Pol mRNA was > 10-fold higher in AIDS-related than in non-AIDS B-lineage lymphomas. beta-Pol expression was up-regulated in a B-cell line upon infection with HIV-1, and increased in Raji cells upon recombinant expression of the Tat gene. The beta-pol promoter was transactivated (fourfold induction) by Tat, but not by Rev. Tat-dependent transactivation required a binding site for the transcription factor Sp1 in the beta-pol promoter. CONCLUSION: These results suggest that HIV-1 Tat can interact with cellular transcription factors to increase the steady-state level of beta-pol in B cells. Tat-mediated induction of beta-pol may alter DNA stability in AIDS-related lymphomas.[1]References
- The HIV-1 transactivator protein Tat is a potent inducer of the human DNA repair enzyme beta-polymerase. Srivastava, D.K., Tendler, C.L., Milani, D., English, M.A., Licht, J.D., Wilson, S.H. AIDS (2001) [Pubmed]
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