HYPERPRODUCTION OF DIHYDROFOLATE REDUCTASE IN DIPLOCOCCUS PNEUMONIAE AFTER MUTATION IN THE STRUCTURAL GENE. EVIDENCE FOR AN EFFECT AT THE LEVEL OF TRANSCRIPTION

Dihydrofolate reductase is markedly hyperproduced in strains of Diplococcus pneumoniae which bear any one of a unique group of sense to sense mutations (amer) in the corresponding structural gene. Increased enzyme levels mediated by the amer mutations are apparently the result of increased rates of de novo synthesis. The basis for these effects could be transcriptional, translational or could involve an increase in messenger RNA stability. Data revealing no difference in stability of the related mRNA in a variety of mutants and the wild-type strain appear to eliminate the last possibility. Other data support the idea of an effect on transcription. This includes the extreme sensitivity of amer mutation expression following genetic transformation, to inhibition by actinomycin D and rifampacin, and the presence in one extremely high level mutant (amer-3 with 120 times the wild-type enzyme content) of increased amounts of mRNA. The data are most compatible with the idea of a regulatory function for the dihydrofolate reductase protein in this organism.