Suppression of retroviral infection by the RAD52 DNA repair protein.

Abstract	Reverse transcription of retroviral RNA into linear double-stranded DNA and its integration into the host cell genome are essential steps in the retroviral life cycle. The nonhomologous end-joining (NHEJ) DNA repair pathway has been implicated in protecting cells from retrovirus-induced apoptosis caused by strand breaks in host cell DNA or unintegrated linear viral DNA. In eukaryotes, both the NHEJ and homologous recombination (HR) pathways play important roles in repairing DNA double-strand breaks. Here we show that the HR repair protein RAD52 modulates the outcome of recombinant HIV-l vector infection by markedly reducing the efficiency of productive integration events. Increased retroviral integration is the first major phenotype described for a RAD52 deficiency in mammalian cells. Mutations in other HR proteins (XRCC2, XRCC3 and BRCA2) do not markedly affect retroviral transduction rates, suggesting that the HR repair pathway per se does not influence retroviral infection. Instead, the mechanism of attenuation of retroviral infection by RAD52 appears to be based upon competition between the RAD52 protein and active integration complexes for the retroviral cDNA genome.
Authors	Alan Lau, Roland Kanaar, Stephen P Jackson, Mark J O'Connor
Journal	The EMBO journal (EMBO J) Vol. 23 Issue 16 Pg. 3421-9 (Aug 18 2004) ISSN: 0261-4189 [Print] England
PMID	15297876 (Publication Type: Journal Article)
Chemical References	Antigens, Nuclear DNA, Viral DNA-Binding Proteins RAD52 protein, human Rad52 DNA Repair and Recombination Protein Rad52 protein, mouse Xrcc6 protein, human Xrcc6 protein, mouse Ku Autoantigen
Topics	Animals Antigens, Nuclear (metabolism) Apoptosis Cell Line DNA Repair DNA, Viral (genetics, metabolism) DNA-Binding Proteins (deficiency, genetics, metabolism) Gene Expression Regulation, Viral HIV Long Terminal Repeat (genetics) HIV-1 (genetics, physiology) Humans Ku Autoantigen Mice Mice, Knockout Rad52 DNA Repair and Recombination Protein Retroviridae (genetics, physiology) Transduction, Genetic Virus Integration (physiology)

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