Abstract
How centrosome removal or perturbations of centrosomal proteins leads to G1 arrest in untransformed mammalian cells has been a mystery. We use microsurgery and laser ablation to remove the centrosome from two types of normal human cells. First, we find that the cells assemble centrioles de novo after centrosome removal; thus, this phenomenon is not restricted to transformed cells. Second, normal cells can progress through G1 in its entirety without centrioles. Therefore, the centrosome is not a necessary, integral part of the mechanisms that drive the cell cycle through G1 into S phase. Third, we provide evidence that centrosome loss is, functionally, a stress that can act additively with other stresses to arrest cells in G1 in a p38-dependent fashion.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Bromodeoxyuridine / metabolism
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Calcium-Binding Proteins / analysis
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Cell Cycle / drug effects
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Cell Cycle / physiology*
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Cell Cycle / radiation effects
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Cells, Cultured
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Centrioles / chemistry
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Centrioles / physiology*
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Centrioles / ultrastructure
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Centrosome / physiology*
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Chromosomal Proteins, Non-Histone / analysis
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Enzyme Inhibitors / pharmacology
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Epithelial Cells / cytology
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Epithelial Cells / metabolism*
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Epithelial Cells / ultrastructure
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G1 Phase / physiology
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Humans
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Imidazoles / pharmacology
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Light
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Microscopy, Electron
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Pyridines / pharmacology
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Calcium-Binding Proteins
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Chromosomal Proteins, Non-Histone
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Enzyme Inhibitors
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Imidazoles
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Pyridines
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caltractin
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p38 Mitogen-Activated Protein Kinases
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Bromodeoxyuridine
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SB 203580