Chromosome movements during mitosis are orchestrated primarily by the interaction of spindle microtubules with the kinetochore 1, the site for attachment of spindle microtubules to the centromere. The kinetochore has an active function in chromosomal segregation through microtubule-based motors located at or near it 1, 2. CENP-E is a microtubule-based kinesin motor 3, and suppression of CENP-E leads to defects characterized by an intact bipolar spindle with several chromosomes clustered close to the poles 4. Studies combining electron microscopic analyses with siRNA-mediated suppression indicated that CENP-E deficiency correlated with a failure of mono-oriented chromosomes to congress to the equator 5, 6. In addition, expression of motorless CENP-E 7, 8, produced a similar failure in achieving metaphase alignment, suggesting the role of CENP-E motor activity in chromosome congression. However, these studies do not specifically and directly address the function of CENP-E motor in chromosome dynamics.

Syntelin does not inhibit progression through S and G2 phases of the cell cycle but causes mitotic arrest with lagging chromosomes, a phenotype reminiscent of what was seen in CENP-E-suppressed cells 4. As expected, inhibition of CENP-E by syntelin did not perturb bipolar spindles but produced misaligned chromosomes near the spindle poles (Figure 1C), similar to those of CENP-E siRNA-treated cells (Supplementary information, Figure S2B). The kinetochore position relative to the pole is an accurate reporter for judging chromosome misalignment (Supplementary information, Figure S2B and S2C; 10), our quantitative analysis indicated a relatively uniform distribution of kinetochores along the length of the spindle in CENP-E-inhibited and CENP-E-suppressed cells (Supplementary information, Figure S2D). Importantly, inhibition of CENP-E motor activity by syntelin resulted in a significant increase in cells bearing misaligned chromosomes (31.7 ± 6.8%; P < 0.05; Supplementary information, Figure S2D), indicating that CENP-E motor activity is essential for faithful chromosome congression.

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