J. Biol. Chem., Vol. 259, Issue 18, 11391-11395, Sep, 1984
Inhibition of the initiation of leukemic transcription by N- trifluoroacetyladriamycin-14-O-hemiadipate in vitro. Impaired formation of RNA polymerase-DNA complex
LF Chuang, M Israel and RY Chuang
The effect of N-trifluoroacetyladriamycin-14-O-hemiadipate (AD 143), a new
derivative of adriamycin, on various steps of the enzymic reaction
catalyzed by chicken myeloblastosis RNA polymerase II was studied. AD 143
inhibition of RNA synthesis, which was evident at the beginning of the
reaction, could not be reversed by increasing the concentrations of any one
of the four nucleoside triphosphate substrates of the reaction.
Furthermore, the RNA synthesis inhibition was not affected by varying the
concentrations of template DNA. The AD 143-induced inhibition caused a
reduction of the frequency of RNA chain initiation, whereas the average
chain length of RNA synthesized at the end of the reaction remained
unaltered. The susceptible step in the initiation process was found to be
the formation of stable complexes between RNA polymerase and the DNA
template. While AD 143 causes no inhibition of Escherichia coli RNA
polymerase activity, it was found not to affect the E. coli RNA
polymerase-template DNA complex formation.
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