Connecting the microtubule attachment status of each kinetochore to cell cycle arrest through the spindle assembly checkpoint.
Kinetochores generate a signal that inhibits anaphase progression until every kinetochore makes proper attachments to spindle microtubules. This spindle assembly checkpoint (SAC) increases the fidelity of chromosome segregation. We will review the molecular mechanisms by which kinetochores generate the SAC and extinguish the signal after making proper attachments, with the goal of identifying unanswered questions and new research directions. We will emphasize recent breakthroughs in how phosphorylation changes drive the activation and inhibition of the signal. We will also emphasize the dramatic changes in kinetochore structure that occur after attaching to microtubules and how these coordinate SAC function with microtubule attachment status. Finally, we will review the emerging cross talk between the DNA damage response and the SAC.
Department of Biochemistry and Molecular Genetics, University of Virginia, School of Medicine, Charlottesville, VA, 22908, USA. pts7h@virginia.edu.
P Todd
PT
Stukenberg
Department of Biochemistry and Molecular Genetics, University of Virginia, School of Medicine, Charlottesville, VA, 22908, USA.
Daniel J
DJ
Burke
D000818:Animals; D004249:DNA Damage; D056890:Eukaryota; D006801:Humans; D018386:Kinetochores / Q000502:physiology*; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology*; D008870:Microtubules; D008941:Spindle Apparatus
Cell division; Chromosome segregation; Mitosis; Mitotic checkpoint