Gap repair completes provirus integration

Stable Identifier
R-HSA-164506
Type
Reaction [dissociation]
Species
Homo sapiens
Related Species
Human immunodeficiency virus 1
Compartment
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The mechanism by which the integration reaction is completed has not been fully clarified. Unfolding of the integration intermediate resulting from the IN-catalyzed transesterification produces a branched DNA molecule. Denaturation of the host DNA between the points of joining produces DNA gaps at each host-virus DNA junction. How these gaps are repaired is unclear. Well studied host cell gap repair enzymes can carry out this repair step on model virus-host DNA junctions in vitro, providing candidate enzymes. However, efforts to show importance in vivo are complicated by the fact that the functions are either redundant or lethal when mutated.

Because the strand transfer complex formed at the completion of integration is quite stable, there may be a requirement for a disassembly step to remove integrase and potentially other proteins to allow access of the gap repair machinery.
In order to complete the last stages of integration, the viral proteins must be removed, and the gaps at the host virus DNA junctions repaired. The sequence in which the dissembly of PIC occus is not yet understood.

Literature References
PubMed ID Title Journal Year
16175173 Genome-wide analysis of retroviral DNA integration

Lewinski, M, Ciuffi, A, Barr, S, Leipzig, J, Hannenhalli, S, Hoffmann, C, Bushman, FD

Nat Rev Microbiol 2005
16291214 Retroviral DNA integration--mechanism and consequences

Lewinski, MK, Bushman, FD

Adv Genet 2005
  Retroviruses

Coffin, JM, Hughes, SH, Varmus, HE

  1997
Participants
Participant Of
Disease
Name Identifier Synonyms
Human immunodeficiency virus infectious disease 526 HIV infection
Authored
Reviewed
Created
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