A Conserved Mechanism for Centromeric Nucleosome Recognition by Centromere Protein CENP-C

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Science  31 May 2013:
Vol. 340, Issue 6136, pp. 1110-1113
DOI: 10.1126/science.1235532

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Kinetochore Targeting

Chromosomes must be segregated accurately during cell division. This is facilitated by the attachment of mitotic spindle microtubules to the kinetochore at the chromosomal centromere. The centromere is marked with the histone H3 variant CenH3 (CENP-A in human), and CENP-C forms part of the inner kinetochore. Kato et al. (p. 1110) used structural biology, biochemistry, and mutagenesis to show that CENP-C recognizes CENP-A chromatin via several different interactions. The CENP-C "central domain" makes close contact with the acidic patch of histones H2A/H2B, and the highly conserved "CENP-C motif" senses both the acidic patch and recognizes the hydrophobicity of the otherwise nonconserved CenH3 tail, supporting a conserved mechanism of centromere targeting by the kinetochore.


Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.

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