Human immunodeficiency virus integrase directs integration to sites of severe DNA distortion within the nucleosome core.
We have examined the consequences of DNA distortion and specific histone-DNA contacts within the nucleosome for integration mediated by the human immunodeficiency virus (HIV)-encoded integrase enzyme. We find that sites of high-frequency integration cluster in the most severely deformed, kinked DNA regions within the nucleosome core. This may reflect either a preference for a wide major groove for association of the integrase or a requirement for target DNA distortion in the DNA strand transfer mechanism. Both the distortion and folding of the target DNA through packaging into nucleosomes may influence the selection of HIV integration sites within the chromosome.
Pruss
D
D
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Bushman
F D
FD
Wolffe
A P
AP
D000818:Animals; D001483:Base Sequence; D002645:Chickens; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004254:DNA Nucleotidyltransferases / Q000302:isolation & purification / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D006678:HIV / Q000201:enzymology* / Q000235:genetics*; D016325:HIV Long Terminal Repeat; D006657:Histones / Q000378:metabolism; D019426:Integrases; D008961:Models, Structural; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis; D013379:Substrate Specificity; D013698:Templates, Genetic; D016662:Virus Integration
D004279:DNA, Viral; D006657:Histones; D009707:Nucleosomes; D009838:Oligodeoxyribonucleotides; D004247:DNA; D004254:DNA Nucleotidyltransferases; D019426:Integrases