| 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
|
| リソース情報 |
| ヒト・動物細胞 |
THP-1(RCB1189) |
