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

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

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

2018
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Overview
The kinetochore proteins CENP-N and CENP-C recognize the histone H3 variant CENP-A in the centromeric nucleosome. This ensures proper kinetochore assembly and accurate segregation of chromosomes. Chittori et al. describe the cryo-electron microscopy structure of the human CENP-A nucleosome-CENP-N complex. The interaction of CENP-N with CENP-A and the nucleosomal DNA together ensure specific and stable centromeric nucleosome recognition. Mutational analyses using both human and Xenopus CENP-A and CENP-N proteins suggest that the proteins have coevolved to preserve the interacting surfaces. Science , this issue p. 339 Cryo–electron microscopy reveals mechanisms of centromeric nucleosome recognition and initial assembly steps of the kinetochore complex. 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–electron microscopy (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 are further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with the coevolution 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.