期刊
CELL DEATH AND DIFFERENTIATION
卷 12, 期 -, 页码 971-978出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4401573
关键词
DNA repair pathways; apoptosis; integrase; NHEJ; DNA damage signaling
资金
- NCI NIH HHS [CA71515, CA06927] Funding Source: Medline
- NIAID NIH HHS [AI40385] Funding Source: Medline
Retroviral DNA integration creates a discontinuity in the host cell chromatin and repair of this damage is required to complete the integration process. As integration and repair are essential for both viral replication and cell survival, it is possible that specific interactions with the host DNA repair systems might provide new cellular targets for human immunodeficiency virus therapy. Various genetic, pharmacological, and biochemical studies have provided strong evidence that postintegration DNA repair depends on components of the nonhomologous end-joining (NHEJ) pathway (DNA-PK (DNA-dependent protein kinase), Ku, Xrcc4, DNA ligase IV) and DNA damage-sensing pathways (Atr (Atm and Rad related), gamma-H2AX). Furthermore, deficiencies in NHEJ components result in susceptibility to apoptotic cell death following retroviral infection. Here, we review these findings and discuss other ways that retroviral DNA intermediates may interact with the host DNA damage signaling and repair pathways.
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