Document 0323
 DOCN  M9550323
 TI    Human immunodeficiency virus reverse transcriptase substitutes for DNA
       polymerase I in Escherichia coli.
 DT    9505
 AU    Kim B; Loeb LA; Joseph Gottstein Memorial Cancer Research Laboratory,
       Department; of Pathology, University of Washington, Seattle 98195.
 SO    Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):684-8. Unique Identifier :
       AIDSLINE MED/95148602
 AB    We present evidence that human immunodeficiency virus (HIV) reverse
       transcriptase (RT) can substitute for DNA polymerase I in bacteria.
       Expression of HIV RT enables an Escherichia coli mutant, polA12 recA718,
       containing a temperature-sensitive mutation in DNA polymerase I, to grow
       at a nonpermissive temperature. The plasmid pBR322 contains a DNA
       polymerase I-dependent origin of replication. Expression of HIV RT
       enables the same E. coli mutant to maintain this plasmid at a
       nonpermissive temperature. Furthermore, expression of HIV RT in this
       mutant renders it sensitive to 3'-azido-3'-deoxythymidine, a commonly
       used anti-AIDS drug that targets HIV RT. These combined findings on the
       genetic complementation of DNA polymerase I by HIV RT provide a
       bacterial assay to screen for drugs directed against HIV RT. Genetic
       complementation provides a method for positive selection of large
       numbers of functional HIV RT mutants for studies on structure-function
       relationships.
 DE    Drug Screening  DNA Polymerase I/*METABOLISM  DNA Replication/DRUG
       EFFECTS  Escherichia coli/DRUG EFFECTS/*ENZYMOLOGY/GENETICS  Genetic
       Complementation Test  Human  HIV/*ENZYMOLOGY  Mutation/PHYSIOLOGY
       Plasmids  Reverse Transcriptase/*METABOLISM  Support, U.S. Gov't, P.H.S.
       Temperature  Zidovudine/PHARMACOLOGY  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).