論文 - 詳細
| RRC ID | 77886 |
|---|---|
| 著者 | Tachiwana H, Shimura M, Nakai-Murakami C, Tokunaga K, Takizawa Y, Sata T, Kurumizaka H, Ishizaka Y. |
| タイトル | HIV-1 Vpr induces DNA double-strand breaks. |
| ジャーナル | Cancer Res |
| 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. |
| 巻・号 | 66(2) |
| ページ | 627-31 |
| 公開日 | 2006-1-15 |
| DOI | 10.1158/0008-5472.CAN-05-3144 |
| PII | 66/2/627 |
| PMID | 16423988 |
| MeSH | Cell Culture Techniques Chromosomes DNA Damage* Gene Products, vpr / physiology* HIV Infections / genetics* HIV Infections / physiopathology* HIV-1 / pathogenicity* Humans Immunocompromised Host vpr Gene Products, Human Immunodeficiency Virus |
| IF | 9.727 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |