Article
- The EMBO Journal (2006) 25, 1295 - 1304
- doi:10.1038/sj.emboj.7601005
Published online: 16 February 2006
Subject Category:
Retroviral DNA integration: reaction pathway and critical intermediates
Min Li1, Michiyo Mizuuchi1, Terrence R Burke Jr2 and Robert Craigie1
- Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
- Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI-Frederick, National Cancer Institute, National Institute of Health, Frederick, MD, USA
Correspondence to:
Robert Craigie, Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg 5, Room 301, National Institutes of Health, 5 Center Drive MSC 0560, Bethesda, MD 20892, USA. Tel.: +301 496 4081; Fax: +301 496 0201; E-mail: bobc@helix.nih.gov
Received 7 October 2005; Accepted 25 January 2006
Abstract
The key DNA cutting and joining steps of retroviral DNA integration are carried out by the viral integrase protein. Structures of the individual domains of integrase have been determined, but their organization in the active complex with viral DNA is unknown. We show that HIV-1 integrase forms stable synaptic complexes in which a tetramer of integrase is stably associated with a pair of viral DNA ends. The viral DNA is processed within these complexes, which go on to capture the target DNA and integrate the viral DNA ends. The joining of the two viral DNA ends to target DNA occurs sequentially, with a stable intermediate complex in which only one DNA end is joined. The integration product also remains stably associated with integrase and likely requires disassembly before completion of the integration process by cellular enzymes. The results define the series of stable nucleoprotein complexes that mediate retroviral DNA integration.
Keywords:
- integrase,
- integration,
- retrovirus,
- transposition
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
The road to chromatin ? nuclear entry of retroviruses
Nature Reviews Microbiology Review (01 Mar 2007)
NEWS AND VIEWS
The HIV integrase catalytic core
Nature Structural Biology News and Views (01 Feb 1995)
Resolving integral questions in site-specific recombination
Nature Structural & Molecular Biology News and Views (01 Aug 2005)
RESEARCH
A large nucleoprotein assembly at the ends of the viral DNA mediates retroviral DNA integration
The EMBO Journal Article (15 Dec 1997)
The EMBO Journal Article (02 Jul 2001)
