Retroviral DNA integration and the DNA damage response.
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.
Skalka
A M
AM
Fox Chase Cancer Center, Institute for Cancer Research, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA. am_skalka@fccc.edu
Katz
R A
RA
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004249:DNA Damage; D004260:DNA Repair; D004279:DNA, Viral / Q000502:physiology*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000502:physiology / Q000821:virology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic; D016662:Virus Integration
D018797:Cell Cycle Proteins; D004279:DNA, Viral; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases