Nonsense suppression in thymine-requiring strains of Escherichia coli is a consequence of altered folate metabolism

Thymine-requiring strains of Escherichia coli suppress nonsense and frameshift mutants of T4 phage. We proposed that these mutants make errors during translation because of an imbalance in folate metabolism. A thymine-requiring strain grown under suppressing conditions has elevated levels of reduced folates. We tested the effect of either mutational blocks or the inhibition of various steps in folate biosynthesis on suppression. Conditions which prevent the accumulation of 5-methyl tetrahydrofolate inhibit suppression, suggesting that elevated levels of this folate are required for suppression. Furthermore, conditions that result in an accumulation in dihydrofolate inhibit suppression.