Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

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

Oncogene volume 23, pages 2664–2671 (2004)Cite this article

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Aguilera A . (2001). Trends Genet., 17, 318–321.

  • Barboric M, Nissen RM, Kanazawa S, Jabrane-Ferrat N and Peterlin BM . (2001). Mol. Cell, 8, 327–337.

  • Baumann P and West SC . (1998). Proc. Natl. Acad. Sci. USA, 24, 14066–14070.

  • Bennasser Y, Badou A, Tkaczuk J and Bahraoui E . (2002). Virology, 303, 174–180.

  • Berkhout B, Verhoef K, Marzio G, Klaver B, Vink M, Zhou X and Das AT . (2002). J. Neurovirol., 8 (Suppl 2), 134–137.

  • Brown KD, Rathi A, Kamath R, Beardsley DI, Zhan Q, Mannino JL and Baskaran R . (2003). Nat. Genet., 33, 80–84.

  • Buonaguro L, Barillari G, Chang HK, Bohan CA, Kao V, Morgan R, Gallo RC and Ensoli B . (1992). J. Virol., 66, 7159–7167.

  • Chen P, Mayne M, Power C and Nath A . (1997). J. Biol. Chem., 272, 22385–22388.

  • Clark E, Santiago F, Deng L, Chong S, de La Fuente C, Wang L, Fu P, Stein D, Denny T, Lanka V, Mozafari F, Okamoto T and Kashanchi F . (2000). J. Virol., 74, 5040–5052.

  • Douek DC, Picker LJ and Koup RA . (2003). Ann. Rev. Immunol., 21, 265–304.

  • Duan L, Ozaki I, Oakes JW, Taylor JP, Khalili K and Pomerantz RJ . (1994). J. Virol., 68, 4302–4313.

  • Esposito G, Ligresti A, Izzo AA, Bisogno T, Ruvo M, Di Rosa M, Di Marzo V and Iuvone T . (2002). J. Biol. Chem., 277, 50348–50354.

  • Featherstone C and Jackson SP . (1999). Mutat. Res., 434, 3–15.

  • Gonzalez E, Punzon C, Gonzalez M and Fresno M . (2001). J. Immunol., 166, 4560–4569.

  • Green MH, Lowe JE, Waugh AP, Aldridge KE, Cole J and Arlett CF . (1994). Mutant Res., 316, 91–102.

  • Kai M and Wang TS . (2003). Genes Dev., 17, 64–76.

  • Kashanchi F, Agbottah ET, Pise-Masison CA, Mahieux R, Duvall J, Kumar A and Brady JN . (2000). J. Virol., 74, 652–660.

  • Kundu M, Sharma S, De Luca A, Giordano A, Rappaport J, Khalili K and Amini S . (1998). J. Biol. Chem., 273, 8130–8136.

  • Lambotte O, Deiva K and Tardieu M . (2003). Brain Pathol., 13, 95–103.

  • Lee SH and Kim CH . (2002). Mol. Cell, 13, 159–166.

  • Li CJ, Wang C, Friedman DJ and Pardee A . (1995). Proc. Natl. Acad. Sci. USA, 92, 5461–5464.

  • Liang C and Wainberg MA . (2002). AIDS Rev., 4, 41–49.

  • Magnusson KP, Sandstrom M, Stahlberg M, Larsson M, Flygare J, Hellgren D, Wiman KG and Ljungquist S . (2000). Gene, 246, 247–254.

  • Mahieux R, Lambert PF, Agbottah E, Halanski MA, Deng L, Kashanchi F and Brady JN . (2001). J. Virol., 75, 1736–1743.

  • McCloskey TW, Ott M, Tribble E, Khan SA, Teichberg S, Paul MO, Pahwa S, Verdin E and Chirmule N . (1997). J. Immunol., 158, 1014–1019.

  • Persaud D, Zhou Y, Siliciano JM and Siliciano RF . (2003). J. Virol., 77, 1659–1665.

  • Peruzzi F, Gordon J, Darbinian N and Amini S . (2002). J. Neurovirol., 8 (Suppl 2), 91–96.

  • Phimister EG . (2003). N. Engl. J. Med., 348, 643–644.

  • Pierce AJ, Johnson RD, Thompson LH and Jasin M . (1999). Genes Dev., 15, 2633–2638.

  • Rappaport J, Joseph J, Croul S, Alexander G, Del Valle L, Amini S and Khalili K . (1999). J. Leukoc. Biol., 65, 458–465.

  • Rautonen N, Rautonen J, Martin NL and Wara DW . (1994). AIDS, 8, 1504–1506.

  • Reynolds L, Ullman C, Moore M, Isalan M, West MJ, Clapham P, Klug A and Choo Y . (2003). Proc. Natl. Acad. Sci. USA, 100, 1615–1620.

  • Sawaya BE, Khalili K, Gordon J, Taube R and Amini S . (2000). J. Biol. Chem., 275, 35209–35214.

  • Sawaya BE, Thatikunta P, Denisova L, Brady J, Khalili K and Amini S . (1998). J. Neuroimmunol., 87, 33–42.

  • Sengupta S, Linke SP, Pedeux R, Yang Q, Farnsworth J, Garfield SH, Valerie K, Shay JW, Ellis NA, Wasylyk B and Harris CC . (2003). EMBO J., 22, 1210–1222.

  • Shi B, Raina J, Lorenzo A, Busciglio J and Gabuzda D . (1998). J. Neurovirol., 4, 281–290.

  • Singh NP, Stephens RE and Schneider EL . (1994). Int. J. Radiat. Biol., 66, 23–28.

  • Venkitaraman AR . (2002). Cell, 108, 171–182.

Download references

Acknowledgements

We thank the past and present members of the Center for Neurovirology and Cancer Biology for their insightful discussion, and sharing of reagents and ideas. We also thank C Schriver for editorial assistance and preparation of this manuscript. This work was made possible by grants awarded by NIH to KK, BS, and SA. TS is a scholar of the Leukemia and Lymphoma Society.

Author information

Authors and Affiliations

  1. Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, 015-96, Philadelphia, 19122, PA, USA

    Galina Chipitsyna, Dorota Slonina, Khwaja Siddiqui, Francesca Peruzzi, Krzysztof Reiss, Bassel E Sawaya, Kamel Khalili & Shohreh Amini

  2. Department of Biology, College of Science and Technology, Center for Biotechnology, 1900 North 12th Street, Philadelphia, 19122, PA, USA

    Tomasz Skorski

Authors
  1. Galina Chipitsyna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dorota Slonina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Khwaja Siddiqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francesca Peruzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomasz Skorski
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Krzysztof Reiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bassel E Sawaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kamel Khalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shohreh Amini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shohreh Amini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chipitsyna, G., Slonina, D., Siddiqui, K. et al. HIV-1 Tat increases cell survival in response to cisplatin by stimulating Rad51 gene expression. Oncogene 23, 2664–2671 (2004). https://doi.org/10.1038/sj.onc.1207417

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207417

Keywords

This article is cited by

Search

Advanced search

Quick links