Novel Specific Inhibitors for Analysis of Eukaryotic Cell Cycle Control
Trichostatin A (TSA), isolated as a potent inducer of differentiation in murine erythroleukemia cells, caused reversible arrest of rat 3Y1 fibroblast proliferation in G1 and G2 phases without any inhibition of macromolecular synthesis. Leptomycin B (LMB), isolated as an agent inducing morphological abnormalities in fungi, also blocks the cell cycle of 3Y1 and fission yeast cells in both Cl and G2. Cells released from the G2-arrest by both drugs entered a new S phase without passage through M phase, resulting in the formation of proliferative tetraploid cells. On the other hand, staurosporine, which we rediscovered as a new inhibitor of the cell cycle blocking Gl and G2, induced synchronous G2/M transition after release from the G2 arrest. These results suggest the presence of two distinct stage in G2, which is divided by a putative commitment point for mitosis. Biochemical and genetic analyses using their resistant mutants suggest that the molecular target of TSA is the histone deacetylase while that of LMB is involved in the cdc2 regulatory network.
KeywordsFission Yeast Macromolecular Synthesis Synchronous Culture Fission Yeast Cell Antifungal Antibiotic
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