HIV-1 Vpr induces DNA double-strand breaks

Hiroaki Tachiwana, Mari Shimura, Chikako Nakai-Murakami, Kenzo Tokunaga, Yoshimasa Takizawa, Tetsutaro Sata, Hitoshi Kurumizaka, Yukihito Ishizaka

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    52 Citations (Scopus)

    Abstract

    Recent observations imply that HIV-1 infection induces chromosomal DNA damage responses. However, the precise molecular mechanism and biological relevance are not fully understood. Here, we report that HIV-1 infection causes double-strand breaks in chromosomal DNA. We further found that Vpr, an accessory gene product of HIV-1, is a major factor responsible for HIV-1-induced double-strand breaks. The purified Vpr protein promotes double-strand breaks when incubated with isolated nuclei, although it does not exhibit endonuclease activity in vitro. A carboxyl-terminally truncated Vpr mutant that is defective in DNA-binding activity is less capable of Vpr-dependent double-strand break formation in isolated nuclei. The data suggest that double-strand breaks induced by Vpr depend on its DNA-binding activity and that Vpr may recruit unknown nuclear factor(s) with positive endonuclease activity to chromosomal DNA. This is the first direct evidence that Vpr induces double-strand breaks in HIV-1-infected cells. We discuss the possible roles of Vpr-induced DNA damage in HIV-1 infection and the involvement of Vpr in further acquired immunodeficiency syndrome-related tumor development.

    Original languageEnglish
    Pages (from-to)627-631
    Number of pages5
    JournalCancer Research
    Volume66
    Issue number2
    DOIs
    Publication statusPublished - 2006 Jan 15

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

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  • Cite this

    Tachiwana, H., Shimura, M., Nakai-Murakami, C., Tokunaga, K., Takizawa, Y., Sata, T., Kurumizaka, H., & Ishizaka, Y. (2006). HIV-1 Vpr induces DNA double-strand breaks. Cancer Research, 66(2), 627-631. https://doi.org/10.1158/0008-5472.CAN-05-3144