SYNTHESIS OF GLUTAMINE, GLYCINE AND L0-FORMYL TETRAHYDROFOLATE IS COREGULATED WITH PURINE BIOSYNTHESIS IN SACCHAROMYCES-CEREVISIAE

Glutamine, glycine and 10-formyl tetrahydrofolate are consumed during de novo purine biosynthesis. We have found that, in Saccharomyces cere visiae, synthesis of these cosubstrates is coregulated with synthesis of enzymes of the purine biosynthetic pathway. Analysis of three genes required for synthesis of glutamine, glycine and 10-formyl tetrahydro folate (GLN1, SHM2 and MTD1, respectively) shows that their expression is repressed by adenine and requires the transcription factors Bas1p and Bas2p. Northern analysis reveals that regulation of SHM2 and MTD1 expression by adenine takes place at the transcriptional level. We als o show that Bas1p and Bas2p bind in vitro to the promoters of the SHM2 and MTD1 genes, and that mutations in the consensus Bas1p binding seq uences strongly affect expression of these genes in vivo. Finally, we have found that a SHM2-lacZ fusion is expressed at a significantly hig her level in a bas2-2 disrupted strain than in bas1-2 or bas1-2 bas2-2 mutant strains. The BAS1-dependent, BAS2-independent expression of SH M2-lacZ suggests that, in the absence of Bas2p, Bas1p can interact wit h another protein partner to activate SHM2 expression.