Metaphase Chromosome Alignment is Sensitive to Dynein-Dependent Forces at the Cell Cortex Public
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Mitotic cell division is the process by which one cell is divided into two. During mitosis a microtubule-based machine is built to organize and physically separate the duplicated mitotic chromosomes. Defects in the mitotic machinery, or in the way microtubules associate with the chromosomes can result in the formation of daughter cells with too many or two few chromosomes. Such changes can compromise cell viability and organismal fitness. Formation of the microtubule-based machine, known as the mitotic spindle, is dependent on the function of molecular motors that walk along and organize the microtubule filaments into a dynamic bipolar structure. Chromosomes interact with the mitotic spindle via protein structures that are built on chromatin called kinetochores. Chromosome movement during mitosis, the satisfaction of the spindle assembly checkpoint that governs mitotic exit, and the fidelity of chromosome segregation are all dependent on the formation and maintenance of proper kinetochore- microtubule attachments. Experimental depletion of Nuf2, a kinetochore protein that promotes stable end-on microtubule attachments, prevents chromosomes from congressing to the metaphase plate and precludes progression to anaphase. Here, I show that simultaneous depletion of Nuf2, together with inhibition of dynein-dependent pulling forces at the cell cortex, enables a partial rescue such that chromosome alignment is improved and progression into anaphase can occur. Together, this work demonstrates that stable kinetochore-microtubule attachments are antagonized by the cortex-localized motor protein dynein.
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