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Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N

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Science  21 Dec 2017:
eaar2781
DOI: 10.1126/science.aar2781

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Abstract

Accurate chromosome segregation requires the proper assembly of kinetochore proteins. A key step in this process is the recognition of the histone H3 variant CENP-A in the centromeric nucleosome by the kinetochore protein CENP-N. We report cryo-EM, biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N. We show that human CENP-N confers binding specificity through interactions with the L1 loop of CENP-A, stabilized by electrostatic interactions with the nucleosomal DNA. Mutational analyses demonstrate analogous interactions in Xenopus, which is further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with co-evolution of CENP-N and CENP-A, and establish the structural basis for recognition of the CENP-A nucleosome to enable kinetochore assembly and centromeric chromatin organization.

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