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 language | English |
|---|---|
| Pages (from-to) | 627-631 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 66 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2006 Jan 15 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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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 journal › Article
}
TY - JOUR
T1 - HIV-1 Vpr induces DNA double-strand breaks
AU - Tachiwana, Hiroaki
AU - Shimura, Mari
AU - Nakai-Murakami, Chikako
AU - Tokunaga, Kenzo
AU - Takizawa, Yoshimasa
AU - Sata, Tetsutaro
AU - Kurumizaka, Hitoshi
AU - Ishizaka, Yukihito
PY - 2006/1/15
Y1 - 2006/1/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=31544471786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31544471786&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-05-3144
DO - 10.1158/0008-5472.CAN-05-3144
M3 - Article
C2 - 16423988
AN - SCOPUS:31544471786
VL - 66
SP - 627
EP - 631
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 2
ER -