       Document 0690
 DOCN  M9590690
 TI    Expression of the human integrase interacting protein (ini1) prevents
       growth of a yeast mutant, rad52, defective in chromosome metabolism.
 DT    9509
 AU    Perkins E; Resnick MA; Laboratory of Molecular Genetics, National
       Institute of; Environmental Health Sciences, NIH, Research Triangle
       Park, NC
 SO    NIH Conf Retroviral Integrase. 1995 Jan 19-20;:(Participants' abstracts
       and posters, abstract no. 8). Unique Identifier : AIDSLINE AIDS/95920029
 AB    The human Ini1 protein was originally identified in a two- hybrid screen
       designed to isolate proteins that might interact with HIV integrase (1).
       Since such proteins may play a significant role in integrase function,
       they are potential targets for modifying integrase activity and possibly
       the progression of HIV infection. In a recent study, the Ini1 gene was
       independently isolated based on its effect when expressed in yeast
       (Perkins, Hashem & Resnick, submitted). The screen was designed to
       isolate human expressed genes (cDNAs) that prevent growth of a mutant,
       rad52, defective in chromosome metabolism. We reasoned that there are
       genes that might act in a dominant-negative fashion so as to kill or
       stop growth of this genetically- sensitized mutant which is altered in
       recombination, DNA repair including double-strand break repair,
       chromosome segregation and DNA replication. Included among the over 1000
       expressed human cDNAs from a cerebellum library that specifically
       prevented growth of the rad52, but not a RAD+ strain, was a cDNA whose
       sequence matched that of the Ini1 gene (1). Since the function of Ini1
       has not been established, we have at hand a biological assay in yeast
       that is providing an opportunity to study in vivo the activity of Ini1
       as well as a means for altering its function in relation to integrase.
       Using a pullback protocol, we have established that Ini1 can kill a
       rad52 deletion mutant within 12 hours after placing cells on
       galactose-inducing medium (the cDNA is under the control of a GAL
       promoter). Based on genetic assays in wild type cells, the mechanism of
       Ini1 action does not appear to involve recombination or mutation. Other
       parameters such as chromosome loss, replication and cell cycle arrest
       are being investigated. We are currently examining the consequences of
       joint expression of Ini1 and integrase in order to develop a biological
       system to characterize their interaction. 1 Kalpana & Goff, PNAS 90
       (1993) 10593; GENBANK accession HSV04847
 DE    Chromatin/*METABOLISM  Chromosomes, Human  DNA
       Nucleotidyltransferases/*METABOLISM  DNA, Viral/CHEMISTRY/*GENETICS
       HIV/ENZYMOLOGY/*GENETICS  HIV Long Terminal Repeat  Nucleic Acid
       Conformation  Virus Integration/*GENETICS  MEETING ABSTRACT

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

