SUMMARY PARAGRAPH for GAL1
The Gal1p galactokinase catalyzes the conversion of alpha-D-galactose to galactose-1-phosphate, a key step in galactose catabolism (6, 7). Gal1p is also required for inducible high-affinity galactose uptake, and can function as a weak transcriptional regulator in the absence of Gal3p (8, 7). Gal1p and Gal3p share 90% amino acid similarity, and insertion of just two amino acids (a serine and an alanine) directly after amino acid 164 confers galactokinase activity on transcriptional regulator Gal3p (9). Overexpression of GAL1 results in activation of Gal4p, and gal1 null mutants are unable to grow on galactose as the sole carbon source (10, 11).
All the galactose structural genes (GAL1, GAL10, GAL7, GAL2) are coordinately regulated at the level of transcription in response to galactose by Gal4p, Gal80p, and Gal3p (6, 12, and reviewed in 13). Regardless of carbon source, the Gal4p transcriptional activator is bound as a dimer to upstream activation sites found in the promoters of the GAL genes. In the presence of galactose, Gal3p sequesters the transcriptional repressor Gal80p in the cytoplasm, thereby relieving inhibition of Gal4p and resulting in GAL gene expression (14). In the absence of galactose, Gal80p remains bound as a dimer, to Gal4p, preventing Gal4p from recruiting other factors of the Pol II transcription machinery (reviewed in 13).
Galactokinase is conserved from E. coli to man (10 and reviewed in 15). Mutations in human GALK1, the functional ortholog of yeast GAL1, lead to galactokinase deficiency/galactosemia II (OMIM), characterized by cataract formation due to galactitol accumulation (reviewed in 15).
Last updated: 2006-09-18