The Wilhelmine E. Key 1989 invitational lecture. Organization and regulation of the qa (quinic acid) genes in Neurospora crassa and other fungi.

In Neurospora crassa, five structural genes and two regulatory genes control the use of quinic acid as a carbon source. All seven genes are tightly linked to form the qa gene cluster. The entire cluster, which has been cloned and sequenced, occupies a continuous DNA segment of 17.3 kb. Three pairs of genes are divergently transcribed, including the two regulatory genes that are located at one end of the cluster and that encode an activator (qa-1F) and a repressor (qa-1S). Three of the structural genes (qa-2, qa-3, and qa-4) encode inducible enzymes that catalyze the catabolism of quinic acid. One structural gene (qa-y) encodes a quinate permease; the function of the fifth gene (qa-x) is still unclear. Present genetic and molecular evidence indicates that the qa activator and repressor proteins and the inducer quinic acid interact to control expression at the transcriptional level of all the qa genes. The activator, the product of the autoregulated qa-1F gene, binds to symmetrical 16 base pair upstream activating sequences located one or more times 5' to each of the qa genes. A conserved 28 amino acid sequence containing a six cysteine zinc binding motif located in the amino terminal region of the activator has been directly implicated in DNA binding. Evidence for other functional domains in the activator and repressor proteins are discussed. Indirect evidence suggests that the repressor is not a DNA-binding protein but forms an inactive complex with the activator in the absence of the inducer.(ABSTRACT TRUNCATED AT 250 WORDS)