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HIV-1 Vpr degrades the HLTF DNA translocase in T cells and macrophages.

Abstract : Viruses often interfere with the DNA damage response to better replicate in their hosts. The human immunodeficiency virus 1 (HIV-1) viral protein R (Vpr) protein has been reported to modulate the activity of the DNA repair structure-specific endonuclease subunit (SLX4) complex and to promote cell cycle arrest. Vpr also interferes with the base-excision repair pathway by antagonizing the uracil DNA glycosylase (Ung2) enzyme. Using an unbiased quantitative proteomic screen, we report that Vpr down-regulates helicase-like transcription factor (HLTF), a DNA translocase involved in the repair of damaged replication forks. Vpr subverts the DDB1-cullin4-associated-factor 1 (DCAF1) adaptor of the Cul4A ubiquitin ligase to trigger proteasomal degradation of HLTF. This event takes place rapidly after Vpr delivery to cells, before and independently of Vpr-mediated G2 arrest. HLTF is degraded in lymphocytic cells and macrophages infected with Vpr-expressing HIV-1. Our results reveal a previously unidentified strategy for HIV-1 to antagonize DNA repair in host cells.
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Contributor : Isma Ziani Connect in order to contact the contributor
Submitted on : Tuesday, September 27, 2016 - 11:11:07 AM
Last modification on : Tuesday, May 31, 2022 - 10:20:15 AM

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Hichem Lahouassa, Marie-Lise Blondot, Lise Chauveau, Ghina Chougui, Marina Morel, et al.. HIV-1 Vpr degrades the HLTF DNA translocase in T cells and macrophages.. Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2016, 113 (19), pp.5311-6. ⟨10.1073/pnas.1600485113⟩. ⟨pasteur-01372385⟩



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