Cell cycle checkpoints: arresting progress in mitosis.
Cell cycle arrest in M phase can be induced by the failure of a single chromosome to attach properly to the mitotic spindle. The same cell cycle checkpoint mediates M phase arrest when cells are treated with drugs that either disrupt or hyperstabilize spindle microtubules. Study of yeast mutants that fail to arrest in the presence of microtubule disruptors identified a set of genes important in this checkpoint pathway. Two recent papers report the cloning of human and Xenopus homologues of one of these yeast genes, called MAD2 (for mitotic arrest deficient-2)(1,2). Introduction of antibodies to the MAD2 protein into living mammalian cells or Xenopus egg extracts abrogates the M phase arrest induced by microtubule inhibitors. This and other recent developments suggest a model for the M phase checkpoint in which unattached kinetochores inhibit the ubiquitination of proteins whose proteolysis is necessary for chromatid separation and exit from mitosis.
Gorbsky
G J
GJ
Dept of Cell Biology, University of Virginia Health Sciences Center, Charlottesville 22908, USA. GJG5y@virginia.edu
D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D006801:Humans; D064246:Mad2 Proteins; D008938:Mitosis / Q000502:physiology*; D012097:Repressor Proteins
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins