Alterations in chromosome dynamics affect the fidelity of chromosome transmission

Abstract

The majority of cancer cells show chromosomal instability (CIN), a condition in which chromosome missegregation occurs at a high rate. As defects in critical mitotic processes are lethal, CIN in cancer cells supposedly arise from defects in non-essential processes that allow cell survival. Merotelic attachment, an erroneous attachment of kinetochores to microtubules, plays a major role in the generation of CIN, by escaping the spindle assembly checkpoint and forming lagging chromosomes that result in chromosome missegregation. We found that efficient chromosome movement towards the spindle equator and subsequent chromosome oscillation around the spindle equator are important for faithful chromosome segregation. We propose that these non-essential processes play a causal role in the generation of CIN through the formation of merotelic attachment.