A key feature of chromosome segregation is the ability to sense tension between sister kinetochores. DNA between sister kinetochores must be packaged in a way that sustains tension propagation from one kinetochore to its sister, approximately 1 micron away. A molecular bottlebrush consisting of a primary axis populated with a crowded array of side chains provides a means to build tension over length scales considerably larger than the stiffness of the individual elements, that is, DNA polymer. Evidence for the bottlebrush organization of chromatin between sister kinetochores comes from genetic, cell biological, and polymer modeling of the budding yeast centromere. In this study, we have used polymer dynamic simulations of the bottlebrush to recapitulate experimental observations of kinetochore structure. Several aspects of the spatial distribution of kinetochore proteins and their response to perturbation lack a mechanistic understanding. Changes in physical parameters of bottlebrush, DNA stiffness, and DNA loops directly impact the architecture of the inner kinetochore. This study reveals that the bottlebrush is an active participant in building tension between sister kinetochores and proposes a mechanism for chromatin feedback to the kinetochore.

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Journal Article | Research Support, N.I.H., Extramural

Authors

Lawrimore J, de Larminat SC, Cook D, Friedman B, Doshi A, Yeh E, Bloom K

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