2-Aminopurine overrides multiple cell cycle checkpoints in BHK cells.
BHK cells blocked at any of several points in the cell cycle override their drug-induced arrest and proceed in the cycle when exposed concurrently to the protein kinase inhibitor 2-aminopurine (2-AP). For cells arrested at various points in interphase, 2-AP-induced cell cycle progression is made evident by arrival of the drug-treated cell population in mitosis. Cells that have escaped from mimosine G1 arrest, from hydroxyurea or aphidicolin S-phase arrest, or from VM-26-induced G2 arrest subsequently have all the hallmarks of mitosis--such as a mitotic microtubule array, nuclear envelope breakdown, and chromatin condensation. In a synchronous population, the time course of arrival in mitosis and its duration in 2-AP-treated cells that have escaped drug-induced cell cycle blocks is indistinguishable from control cells. Cells arrested in mitosis by nocodazole or taxol quickly escape mitotic arrest and enter interphase when exposed to 2-AP. 2-AP by itself does not influence the timing of cell cycle progression. We conclude that 2-AP acts to override checkpoints in every phase of the cell cycle, perhaps by inhibiting a protein kinase responsible for control of multiple cell cycle checkpoints.
Andreassen
P R
PR
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Margolis
R L
RL
D015075:2-Aminopurine / Q000494:pharmacology*; D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000032:analysis; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D008898:Mimosine / Q000494:pharmacology; D008940:Mitotic Index; D047428:Protein Kinase Inhibitors; D013713:Teniposide / Q000494:pharmacology; D013997:Time Factors
D047428:Protein Kinase Inhibitors; D016590:Aphidicolin; D015075:2-Aminopurine; D008898:Mimosine; D004247:DNA; D013713:Teniposide; D006918:Hydroxyurea