Document 0688
 DOCN  M9590688
 TI    On the structural determinants of hiv integration into chromatin.
 DT    9509
 AU    Pruss FD; Bushman D; Wolffe AP; NICHD/NIH, Bethesda MD
 SO    NIH Conf Retroviral Integrase. 1995 Jan 19-20;:(Participants' abstracts
       and posters, abstract no. 10). Unique Identifier : AIDSLINE
       AIDS/95920031
 AB    Integration of the HIV DNA into the human chromosomes is a necessary
       step in the viral lifecycle. Nucleosomal DNA is known to be accepted and
       even preferred as the target by the viral integration machinery. We used
       purified HIV integrase, a synthetic LTR-like substrate and a number of
       nucleosomal and free DNA integration targets of various defined
       structures to investigate the molecular basis of selectivity of the
       integration reaction vitro. We show that HIV integrase preferentially
       targets bent DNAs. Integration events localize on the outer side of the
       bends, i.e. where the target DNA is bent away from the enzyme. Both
       intrinsic and histone-indiced DNA bending affects integration in the
       same way. More severely distorted DNA segments afford more integration
       events. Flexible DNA sequences are relatively preferred by the
       integrase, even in unfavorable steric surrounding. Rigid DNA sequences
       are underutilized even after being bent within the nucleosomes. The
       remarkable DNA structure sensitivity and virtual absence of sequence
       specificity of the integration make the integrase a unique footprinting
       tool.
 DE    Acquired Immunodeficiency Syndrome/DRUG THERAPY  Antiviral
       Agents/THERAPEUTIC USE  *DNA Nucleotidyltransferases/*ANTAGONISTS &
       INHIB  Enzyme Inhibitors/CHEMISTRY/*PHARMACOLOGY  HIV-1/*ENZYMOLOGY
       Models, Molecular  Recombinant Proteins  Structure-Activity Relationship
       MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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