HIV-1 Tat increases cell survival in response to cisplatin by stimulating Rad51 gene expression

Oncogene. 2004 Apr 8;23(15):2664-71. doi: 10.1038/sj.onc.1207417.


Tat is an early regulatory protein of human immunodeficiency virus type 1, which plays a central role in the pathogenesis of AIDS by stimulating transcription of the viral genome and impairing several important cellular pathways during the progression of the disease. Here, we investigated the effect of Tat on cell response to DNA damage. Our results indicate that Tat production causes a noticeable increase in the survival rate of PC12 cells upon their treatment with genotoxic agents. Single-cell gel electrophoresis studies revealed reduced DNA breakage in PC12-Tat cells upon cisplatin treatment relative to the control cells. Furthermore, cytogenetic data exhibited less chromosomal damage in Tat-producing cells after recovery from cisplatin treatment, corroborating electrophoretic data. Examination of several proteins involved in the control of DNA repair showed elevated levels of Rad51, a key regulator of homologous recombination in cells expressing Tat. On the other hand, the level of Ku70, one of the components of the nonhomologous end-joining repair pathway, was slightly decreased in cells expressing Tat. Using a fluorescence-based assay, we demonstrated that repair of DNA double-strand breaks via homologous recombination is increased in Tat-producing cells. The results from in vitro nonhomologous end-joining assay revealed a reduced ability of protein extract from PC12-Tat cells compared to PC12 cells in rejoining linearized DNA. These observations ascribe a new role for Tat in host genomic integrity, perhaps by affecting the expression of genes involved in DNA repair.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Nuclear / biosynthesis
  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Cell Survival
  • Chromosome Aberrations
  • Cisplatin / pharmacology*
  • Comet Assay
  • DNA Damage
  • DNA Repair
  • DNA, Complementary / metabolism
  • DNA-Binding Proteins / biosynthesis*
  • Gene Products, tat / metabolism
  • Gene Products, tat / physiology*
  • Genes, Reporter
  • Ku Autoantigen
  • Luciferases / metabolism
  • PC12 Cells
  • Plasmids / metabolism
  • Rad51 Recombinase
  • Rats
  • Time Factors
  • Transcriptional Activation


  • Antigens, Nuclear
  • Antineoplastic Agents
  • DNA, Complementary
  • DNA-Binding Proteins
  • Gene Products, tat
  • Luciferases
  • Rad51 Recombinase
  • Rad51 protein, rat
  • Xrcc6 protein, human
  • Xrcc6 protein, rat
  • Ku Autoantigen
  • Cisplatin