During mitosis, tension develops across the centromere as a result of spindle-based forces. Metaphase tension may be critical in preventing mitotic chromosome segregation errors, however, the nature of force transmission at the centromere and the role of centromere mechanics in controlling metaphase tension remains unknown. We combined quantitative, biophysical microscopy with computational analysis to elucidate the mechanics of the centromere in unperturbed, mitotic human cells. We discovered that the mechanical stiffness of the human centromere matures during mitotic progression, which leads to amplified centromere tension specifically at metaphase. Centromere mechanical maturation is disrupted across multiple aneuploid cell lines, leading to a weak metaphase tension signal. Further, increasing deficiencies in centromere mechanical maturation are correlated with rising frequencies of lagging, merotelic chromosomes in anaphase, leading to segregation defects at telophase. Thus, we reveal a centromere maturation process that may be critical to the fidelity of chromosome segregation during mitosis.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health grant F30 CA223591 to L.A.H., National Institutes of Health grant NIGMS GM-103833 and National Science Foundation CAREER award 1350741 to M.K.G., and National Institutes of Health grant T32 GM008244 to the University of Minnesota MSTP. We thank Drs. Pete Bitterman, Daniela Cimini, Duncan Clarke, Eric Van Dyck, Tom Hayes, Judith Ber-man, Alexey Khodjakov, Helder Maiato, Andrew McAinsh, Wolfgang Nellen, and Meg Titus for gifting reagents and cell lines used as part of this project. We thank Drs. Alexey Khodjakov, Beth Sullivan, Duncan Clarke, and Meg Titus, and the Gardner Laboratory, in particular Soumya Mukherjee and Dr. Jeremy Chacon, for helpful discussions.
© 2019, The Author(s).