Integration of human immunodeficiency virus DNA: adduct interference analysis of required DNA sites.
The integration (IN) protein encoded by human immunodeficiency virus directs the integration of viral DNA into host DNA. We have probed the DNA sites required for the function of IN protein by attaching adducts to model DNA substrates and assaying their effects on integration in vitro. These experiments reveal that modifications in a short region on both DNA strands at the ends of the viral DNA block IN protein function. Modification of the target DNA near the point of DNA strand transfer also blocks IN protein function. Further experiments suggest that distinct subsets of the identified interactions are important for separate steps in the integration process.
Bushman
F D
FD
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Craigie
R
R
D001345:Autoradiography; D010584:Bacteriophage phi X 174 / Q000235:genetics; D001483:Base Sequence; D004254:DNA Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005038:Ethylnitrosourea / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects / Q000235:genetics*; D016325:HIV Long Terminal Repeat; D019426:Integrases; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010761:Phosphorus Radioisotopes; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D016662:Virus Integration / Q000187:drug effects
D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D010761:Phosphorus Radioisotopes; D011994:Recombinant Proteins; D004254:DNA Nucleotidyltransferases; D019426:Integrases; D005038:Ethylnitrosourea