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

    Research output: Contribution to journalArticle

    51 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

    Fingerprint

    Double-Stranded DNA Breaks
    HIV-1
    HIV Infections
    Endonucleases
    DNA
    DNA Damage
    vpr Gene Products
    Chromosome Breakage
    Acquired Immunodeficiency Syndrome
    Neoplasms

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Tachiwana, H., Shimura, M., Nakai-Murakami, C., Tokunaga, K., Takizawa, Y., Sata, T., ... 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

    HIV-1 Vpr induces DNA double-strand breaks. / Tachiwana, Hiroaki; Shimura, Mari; Nakai-Murakami, Chikako; Tokunaga, Kenzo; Takizawa, Yoshimasa; Sata, Tetsutaro; Kurumizaka, Hitoshi; Ishizaka, Yukihito.

    In: Cancer Research, Vol. 66, No. 2, 15.01.2006, p. 627-631.

    Research output: Contribution to journalArticle

    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, vol. 66, no. 2, pp. 627-631. https://doi.org/10.1158/0008-5472.CAN-05-3144
    Tachiwana H, Shimura M, Nakai-Murakami C, Tokunaga K, Takizawa Y, Sata T et al. HIV-1 Vpr induces DNA double-strand breaks. Cancer Research. 2006 Jan 15;66(2):627-631. https://doi.org/10.1158/0008-5472.CAN-05-3144
    Tachiwana, Hiroaki ; Shimura, Mari ; Nakai-Murakami, Chikako ; Tokunaga, Kenzo ; Takizawa, Yoshimasa ; Sata, Tetsutaro ; Kurumizaka, Hitoshi ; Ishizaka, Yukihito. / HIV-1 Vpr induces DNA double-strand breaks. In: Cancer Research. 2006 ; Vol. 66, No. 2. pp. 627-631.
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