title: Kinetochore-microtubule attachment is sufficient to satisfy the human spindle assembly checkpoint.
abstract: The spindle assembly checkpoint (SAC) is a genome surveillance mechanism that protects against aneuploidization. Despite profound progress on understanding mechanisms of its activation, it remains unknown what aspect of chromosome-spindle interactions is monitored by the SAC: kinetochore-microtubule attachment or the force generated by dynamic microtubules that signals stable biorientation of chromosomes? To answer this, we uncoupled these two processes by expressing a non-phosphorylatable version of the main microtubule-binding protein at kinetochores (HEC1-9A), causing stabilization of incorrect kinetochore-microtubule attachments despite persistent activity of the error-correction machinery. The SAC is fully functional in HEC1-9A-expressing cells, yet cells in which chromosomes cannot biorient but are stably attached to microtubules satisfy the SAC and exit mitosis. SAC satisfaction requires neither intra-kinetochore stretching nor dynamic microtubules. Our findings support the hypothesis that in human cells the end-on interactions of microtubules with kinetochores are sufficient to satisfy the SAC without the need for microtubule-based pulling forces.
authors.affiliation: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
authors.forename: Banafsheh
authors.initials: B
authors.lastname: Etemad
authors.affiliation: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
authors.forename: Timo E F
authors.initials: TE
authors.lastname: Kuijt
authors.affiliation: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.|Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.|Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.|Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
authors.forename: Geert J P L
authors.initials: GJ
authors.lastname: Kops
mesh_terms: D020090:Chromosome Segregation; D003598:Cytoskeletal Proteins; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins