title: Spindle assembly checkpoint: the third decade.
abstract: The spindle assembly checkpoint controls cell cycle progression during mitosis, synchronizing it with the attachment of chromosomes to spindle microtubules. After the discovery of the mitotic arrest deficient (MAD) and budding uninhibited by benzymidazole (BUB) genes as crucial checkpoint components in 1991, the second decade of checkpoint studies (2001-2010) witnessed crucial advances in the elucidation of the mechanism through which the checkpoint effector, the mitotic checkpoint complex, targets the anaphase-promoting complex (APC/C) to prevent progression into anaphase. Concomitantly, the discovery that the Ndc80 complex and other components of the microtubule-binding interface of kinetochores are essential for the checkpoint response finally asserted that kinetochores are crucial for the checkpoint response. Nevertheless, the relationship between kinetochores and checkpoint control remains poorly understood. Crucial advances in this area in the third decade of checkpoint studies (2011-2020) are likely to be brought about by the characterization of the mechanism of kinetochore recruitment, activation and inactivation of checkpoint proteins, which remains elusive for the majority of checkpoint components. Here, we take a molecular view on the main challenges hampering this task.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy. andrea.musacchio@mpi-dortmund.mpg.de
authors.forename: Andrea
authors.initials: A
authors.lastname: Musacchio
mesh_terms: D000818:Animals; D064127:Aurora Kinases; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry*; D019926:Cyclin B / Q000737:chemistry; D004789:Enzyme Activation; D006801:Humans; D018386:Kinetochores / Q000737:chemistry*; D059566:M Phase Cell Cycle Checkpoints; D046912:Multiprotein Complexes / Q000737:chemistry; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry; D015398:Signal Transduction; D008941:Spindle Apparatus
chemical_list: D018797:Cell Cycle Proteins; D019926:Cyclin B; D046912:Multiprotein Complexes; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases
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