PROLIFERATION-DEPENDENT DIFFERENTIAL REGULATION OF THE DOLICHOL PATHWAY GENES IN SACCHAROMYCES-CEREVISIAE

The dolichol pathway serves in the synthesis of the dolichol-linked ol igosaccharide precursor for protein N-glycosylation, Recently, we repo rted that mRNAs of genes that function at the early steps in the dolic hol pathway in yeast, ALG7, ALG1 and ALG2, were co-ordinately induced following growth stimulation of G(0)-arrested cells in a manner simila r to that of the transcripts of the early growth response genes (Kukur uzinska,M.A. and Lennon,K. Glycobiology, 4, 437-443, 1994), To determi ne whether the entire dolichol pathway was co-ordinately regulated wit h growth, we examined the expression of genes functioning late in the pathway, including two genes encoding oligosaccharyltransferase subuni ts, at two critical control points in the G(1) phase of cell cycle: G( 0)/G(1) and START, We show that early in G(1), at the G(0)/G(1) transi tion point, the late ALG genes and the two oligosaccharyltransferase-e ncoding genes examined were regulated co-ordinately with the early ALG genes: they were downregulated upon exit from the mitotic cell cycle into Go, and they were induced following growth stimulation in the abs ence of de novo protein synthesis, All the dolichol pathway genes prod uced transcripts with short.half-lives that were rapidly stabilized in the presence of cycloheximide. In contrast, cell division arrest late in G(1), at START, was accompanied by a selective downregulation of o nly the first dolichol pathway gene, ALG7, and not of the genes functi oning later in the pathway, These results indicate that, depending on their position in G(1), cells either co-ordinately or differentially r egulate the dolichol pathway genes.