DDA3 associates with MCAK and controls chromosome congression

DDA3 regulates spindle microtubule (MT) dynamics and chromosome movement in mitosis through its interaction with and subsequent recruitment of Kif2a, a minus end-MT depolymerase. Depletion of DDA3 causes a hyper-stabilization of spindle MT, a loss of inter-kinetochore tension, and a defect in chromosome congression, leading to unaligned chromosomes at metaphase. We report here that DDA3 is also localized at kinetochores and interacts with MCAK. Furthermore, CENP-E, a plus end-motor protein, accumulates at kinetochores in unaligned chromosomes in mitotic cells depleted of DDA3. On the other hand, the localization of chromosomal passenger complex (CPC) and the kinase activity of Aurora B are normal in DDA3-depleted cells. We conclude that MCAK and CENP-E are involved in DDA3-mediated chromosome congression.

► DDA3 localizes to the mitotic kinetochore.
► DDA3 interacts with MCAK.
► CENP-E is accumulated at the mitotic kinetochore in unaligned chromosome caused by DDA3 depletion.
► DDA3 is involved in CENP-E dependent chromosome gliding.