Document 0716
 DOCN  M9590716
 TI    HIV preintegration complexes
 DT    9509
 AU    Miller MD; Wang B; Bushman FD
 SO    NIH Conf Retroviral Integrase. 1995 Jan 19-20;:(Session I, speakers'
       abstracts - unpaged). Unique Identifier : AIDSLINE AIDS/95920003
 AB    In cells freshly infected by HIV, the viral cDNA can be found complexed
       with viral proteins in an integration- competent complex. We have been
       purifying such complexes and studying their composition and function. We
       have confirmed previous work in determining that the complexes are very
       high molecular weight and contain at least a hundred integrase monomers.
       Analysis of the behavior of preintegration complexes in gel filtration
       and density gradient sedimentation indicates that the particles are
       nonspherical in shape. A careful study of the structure of the viral
       cDNA contained in active complexes revealed that the viral DNA contains
       discontinuities, and that these discontinuities can be found in
       integration products. These data indicate that viral DNA synthesis is
       probably not completed until after integration, perhaps by the same host
       DNA repair system that connects the viral 5' ends to host DNA. We have
       also probed the mechanism of capture of target DNA. In principle,
       preintegration complexes of integrase assembled with LTR DNAs in vitro
       could associate with target DNA by any of three pathways: complexes
       might bind and release target DNA and slide along it before integrating,
       or complexes might bind tightly to target and integrate at the point of
       initial association. We find that the presence of host factors can
       influence this process. In experiments in which two integration targets
       are added sequentially, partially purified preintegration complexes
       associate tightly and irreversibly to the first target added, whereas in
       the presence of host fractions no such fast association is seen.
 DE    Chromatography, Gel  DNA Nucleotidyltransferases/METABOLISM  DNA Repair
       DNA, Complementary/GENETICS  DNA, Viral/GENETICS/METABOLISM
       HIV/ENZYMOLOGY/*GENETICS  HIV Long Terminal Repeat  Molecular Weight
       Virus Integration/*GENETICS  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).