Nucleoporin Tpr interacts with dynein preventing chromosome lagging formation

Gain or loss of whole chromosomes is often found in cancer cells and is thought to be due to aberrant chromosome segregation during mitosis. Proper chromosome segregation depends on a faithful interaction between spindle microtubules and kinetochores. Several components of the nuclear pore complex (NPC)/nucleoporins play critical roles in orchestrating the rapid remodeling events that occur during mitosis. We show here that association of a nucleoporin, termed Tpr (translocated promoter region), with the molecular motors, dynein and dynactin, which both orchestrate with the spindle checkpoints Mad1 and Mad2 during cell division. Over‐expression of Tpr enhanced multinucleated cell formation. RNAi‐mediated knockdown of Tpr caused a severe lagging chromosome phenotype and disrupted spindle checkpoint proteins expression and localization. Our data indicate that Tpr functions as a spatial and temporal regulator of spindle checkpoints, ensuring the efficient recruitment of checkpoint proteins to the molecular motor dynein to ensure proper anaphase formation.