THE ROLE OF DEOXYRIBONUCLEIC ACID SYNTHESIS IN DEATH CAUSED BY STARVATION FOR BIOTIN IN THE YEAST, SACCHAROMYCES CEREVISIAE

Abstract

The effect of hydroxyurea on the death resulting from biotin starvation was examined. This chemical, which preferentially inhibits deoxyribonucleic acid (DNA) replication in the yeast Saccharomyces cerevisiae, prevented death after biotin starvation. Hydroxyurea also inhibits DNA synthesis. Growth, ribonucleic acid (RNA) synthesis, and protein synthesis were less sensitive to this chemical. Cell death was strongly suppressed on addition of 0.2M hydroxyurea when the cells were simultaneously starved for biotin.
At this concentration, DNA synthesis was selectively inhibited, while RNA and protein syntheses continued at nearly the control rate for 8hr of cultivation. In the subculture from which hydroxyurea was removed after 8hr of growth, DNA synthesis was resumed abruptly and cell death occurred without any lag. Furthermore, as the timing of addition of hydroxyurea into the biotin-free medium containing aspartic acid (Asp medium) was delayed, the rate of cell death increased proportionally. On the other hand, when hydroxyurea was added at 0.2M to the Asp medium, cells underwent one cycle of budding, but neither the nucleus nor the cell divided. In the presence of hydroxyurea at 0.2M, the incorporation of acetate [U-¹⁴C] into the lipid fraction of the cells was almost the same as the control without hydroxyurea even after 8hr of cultivation. These results indicate that death resulting from unbalanced growth did not occur when DNA synthesis was inhibited, even though macromolecular substances and buds were normally produced under the biotin-deficient condition.