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Trends Biochem Sci. 2013 Jun;38(6):302-11. doi: 10.1016/j.tibs.2013.03.004. Epub 2013 Apr 16.

Tracking spindle checkpoint signals from kinetochores to APC/C.

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1
Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.

Abstract

Accurate chromosome segregation during mitosis is critical for maintaining genomic stability. The kinetochore--a large protein assembly on centromeric chromatin--functions as the docking site for spindle microtubules and a signaling hub for the spindle checkpoint. At metaphase, spindle microtubules from opposing spindle poles capture each pair of sister kinetochores, exert pulling forces, and create tension across sister kinetochores. The spindle checkpoint detects improper kinetochore-microtubule attachments and translates these defects into biochemical activities that inhibit the anaphase-promoting complex or cyclosome (APC/C) throughout the cell to delay anaphase onset. A deficient spindle checkpoint leads to premature sister-chromatid separation and aneuploidy. Here, we review recent progress on the generation, propagation, transmission, and silencing of the spindle checkpoint signals from kinetochores to APC/C.

PMID:
23598156
DOI:
10.1016/j.tibs.2013.03.004
[Indexed for MEDLINE]
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