Principles of Biochemistry Volume 3 - A. Lehninger 1985

Molecular mechanisms of genetic information transfer
DNA replication and transcription
DNA-dependent RNA polymerase can be selectively inhibited

RNA chain elongation by RNA polymerase is specifically inhibited by the antibiotic actinomycin D in both PROKARYOTES AND EUKARYOTES (Fig. 28-18). The planar portion of this antibiotic molecule intercalates into the DNA double helix between adjacent G-C Base Pairs, thereby distorting the DNA template. This local distortion impedes the movement of the polymerase along the template. Thus, actinomycin D acts somewhat like a “zipper getting stuck.” Because actinomycin D inhibits RNA elongation in both intact Cells and Cell extracts, it has proven to be a very useful diagnostic tool for identifying cellular processes that depend on RNA Synthesis. Another intercalating inhibitor is acridine, whose molecules also possess a planar Structure.

Another important antibiotic that inhibits RNA synthesis is rifampicin, which binds to the ß subunit of prokaryotic RNA polymerase and prevents the initiation of RNA synthesis. However, rifampicin does not inhibit RNA synthesis in eukaryotes. A specific inhibitory effect on RNA synthesis in animal cells is exerted by a-amanitin, the toxic principle of the poisonous mushroom Amanita phalloides. This inhibitor blocks Messenger RNA synthesis carried out by eukaryotic RNA polymerase II, but does not affect RNA synthesis in prokaryotes. Amanita phalloides “acts wisely” by producing a substance that disrupts RNA synthesis in other eukaryotic organisms while remaining harmless to its own transcriptional machinery.

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Fig. 28-18. Structure of actinomycin D, an inhibitor of Introduction/24.html">DNA METABOLISM/31.html">Transcription. The portion of the molecule shown on a red Background intercalates into the double-stranded DNA helix, inserting itself between two adjacent G-C base pairs. The two cyclic peptide structures of the actinomycin D molecule reside in the minor groove of The Double Helix. Sarcosine is N-methylglycine. Sarcosine, L-Proline, and D-valine are linked to each other by peptide bonds.