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'Blueprint for kinetochores: How cells establish functional kinetochores for faithful chromosome segregation'

Feb 12, 2018 - 4:10 PM
to Feb 12, 2018 - 5:00 PM
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Aussie Suzuki.
Aussie Suzuki

Aussie Suzuki — University of North Carolina at Chapel Hill, Department of Biology, Postdoctoral Fellow

Abstract: Chromosome segregation is a fundamental feature that allows all organisms to maintain cell proliferation. Failure of chromosome segregation leads to carcinogenesis, developmental diseases, and apoptotic cell death. To achieve accurate chromosome segregation, the microtubule must be properly captured by a macro-molecular protein complex on the chromosome called a kinetochore. Kinetochores serve as the platform for microtubule assembly and play a critical role in force production/transmission, checkpoint control, and error correction for proper chromosome segregation. Core kinetochore architecture is built by at least 25 different kinds of proteins, but how these core-structural proteins establish functional kinetochores is largely unsolved. To answer this question, I have developed a method to determine the mean 3D kinetochore protein positions with nm-scale accuracy using light microscopy. I found that proper kinetochore functions in error correction and microtubule assembly require nm-scale control, and if the kinetochore stretches ~60 nm more than normal, the kinetochore is not able to assemble microtubules properly anymore. Next, to address the question of how many core-structural proteins are required to build a functional kinetochore, I have also developed a method to determine cellular protein copy number and protein stoichiometry using light microscopy. This quantitative approach revealed that the single human kinetochore has ~240 molecules of Ndc80, which is a highly-conserved microtubule associated protein (MAP) and plays a major role in force coupling at kinetochores. My quantitative method also revealed the stoichiometry of how Ndc80 is recruited to the kinetochore by other core-structural proteins. These results elucidate the blueprint for human kinetochores.

Host: Moe Gupta

Refreshments will be served outside Room 1414 in the Molecular Biology Building before the seminar at 3:45 p.m.