Induction of partial mitosis in BHK cells by 2-aminopurine.
The protein kinase inhibitor 2-aminopurine (2-AP) inhibits a subset of mitotic events in BHK cells. In the presence of the drug, these cells form a bipolar spindle in mitosis, but chromatin fails to generate functioning chromosomes. Cells in 2-AP progress through a partial mitosis, in which there is no observable metaphase, anaphase or telophase events. After 12 h of exposure to 2-AP the chromatin in mitotic cells fails to condense into discrete chromosomes, and is displaced by the spindle to form 'binucleate' cells and cells containing abnormally shaped nuclei in the subsequent interphase. Other mitotic modifications of nuclei, such as nucleolar and nuclear lamina disassembly, occur normally. Centromeres in these nuclei do not become engaged in the spindle, but instead show either no association or a lateral arrangement around the spindle. Cells treated with 2-AP are not arrested in mitosis. Therefore, mitotic exit is not inhibited by the failure of these cells to progress through the latter stages of mitosis. Further, nocodazole-arrested cells quickly exit mitotic arrest when 2-AP is added. We conclude that 2-AP interferes with a specific subset of mitotic events, and that it allows cells to overcome check-points that require spindle function for mitotic progression.
Andreassen
P R
PR
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Margolis
R L
RL
D015075:2-Aminopurine / Q000494:pharmacology*; D000705:Anaphase; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D006224:Cricetinae; D008677:Metaphase; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000187:drug effects*; D008954:Models, Biological; D015739:Nocodazole / Q000037:antagonists & inhibitors; D008941:Spindle Apparatus / Q000187:drug effects; D013692:Telophase
D015075:2-Aminopurine; D016203:CDC2 Protein Kinase; D015739:Nocodazole