Tension Management in the Kinetochore

The kinetochore is the protein machine built at the centromere that integrates mechanical force and chemical energy from dynamic microtubules into directed chromosome motion. The kinetochore also provides a powerful signaling function that is able to alter the properties of the spindle checkpoint and initiate a signal transduction cascade that leads to inhibition of the anaphase promoting complex and cell cycle arrest. Together, the kinetochore accomplishes the feat of chromosome segregation with unparalleled accuracy. Errors in segregation lead to Down's syndrome, the most frequent inherited birth defect, pregnancy loss, and cancer. Over a century after the discovery of the kinetochore, an architectural map comprising greater than 100 proteins is emerging. Understanding the architecture and physical biology of the key components provides new insights into how this fascinating machine moves genomes.