       Document 0511
 DOCN  M9610511
 TI    Human immunodeficiency virus type 1 reverse transcriptase tG:T mispair
       formation on RNA and DNA templates with mismatched primers: a kinetic
       and thermodynamic study.
 DT    9601
 AU    Sala M; Wain-Hobson S; Schaeffer F; Unite de Retrovirologie Moleculaire,
       Institut Pasteur, Paris,; France.
 SO    EMBO J. 1995 Sep 15;14(18):4622-7. Unique Identifier : AIDSLINE
       MED/96003642
 AB    The relationship between human immunodeficiency virus (HIV) type 1
       reverse transcriptase tG:T mispair formation and base pair stability was
       investigated using DNA and RNA templates with 15 bp matched or
       mismatched DNA primers. tG:T mispair formation during primer elongation
       was undetectable on tDNA-DNA duplexes but occurred with a frequency of
       10(-4) on matched tRNA-DNA duplexes. The frequency increased to 7.0 x
       10(-4) and 1.3 x 10(-3) on tRNA-DNA duplexes with tG:T mismatches
       located 6 and 9 bp beyond the polymerization site. From Km values at 37
       degrees C, the free energy change upon dissociation (delta G degrees 37)
       of the tG:T mispair increased from matched to mismatched tRNA-DNA
       duplexes by 0.36-1.21 kcal/mol. delta G degrees 37 for a correct tG:C
       pair decreased by 0.06-1.00 kcal/mol. In comparison with DNA-DNA
       duplexes, thermal melting measurements on RNA-DNA duplexes demonstrated
       smaller enthalpy (delta delta H degrees = -17.7 to 28.1 kcal/mol) and
       entropy (delta delta S degrees = -59.3 to 83.4 cal/mol/K) components. A
       strong entropy-enthalpy compensation resulted in small free energy
       differences (delta delta G degrees 37 = 0.8 to -2.2 kcal/mol). Thus,
       although DNA-DNA and RNA-DNA duplexes are of comparable stability in
       solution, the RNA-DNA duplex presents more facile base pair opening and
       higher conformational flexibility. The release of helical strain at
       constant helix stability in RNA-DNA duplexes may facilitate base
       mispairing during reverse transcription, particularly in the context of
       lentiviral G-->A hypermutation.
 DE    Base Composition  Base Sequence  Comparative Study
       DNA/CHEMISTRY/*GENETICS  *DNA Primers  Kinetics  Molecular Sequence Data
       Nucleic Acid Denaturation  Nucleic Acid Heteroduplexes/CHEMISTRY
       Oligodeoxyribonucleotides/GENETICS  Oligoribonucleotides/GENETICS
       RNA/CHEMISTRY/*GENETICS  RNA-Directed DNA Polymerase/*METABOLISM
       Substrate Specificity  Support, Non-U.S. Gov't  Thermodynamics
       *Transcription, Genetic  JOURNAL ARTICLE

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

