THE INFLUENCE OF DNA AND NUCLEOSOME STRUCTURE ON INTEGRATION EVENTS DIRECTED BY HIV INTEGRASE

DNA copies of the human immunodeficiency virus (HIV) genome integrate nonrandomly into the chromosomal DNA of the host cell. In this report, we investigate the molecular basis of this selectivity using the viru s-encoded HIV integrase to direct integration of a synthetic HIV long terminal repeat substrate into either DNA molecules of known structure or previously defined nucleosomal complexes. We find that the structu re of the target greatly influences the site of integration, and, more over, DNA curvature, flexibility, and rigidity in solution all influen ce the frequency of integration. Importantly, for DNA with all of thes e properties, the distortion of the double helix directed by associati on with the histone proteins promotes the integration reaction and alt ers the distribution of sites that are selected for integration. We su ggest that both intrinsic DNA structure and the folding of DNA into ch romosomal structures will exert a major influence on target site selec tion for integration of the viral genome.