Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome

Science. 2022 May 20;376(6595):844-852. doi: 10.1126/science.abn3810. Epub 2022 Apr 14.


Kinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-ANuc) to mediate attachments between chromosomes and the mitotic spindle. We describe cryo-electron microscopy structures of the human inner kinetochore constitutive centromere associated network (CCAN) complex bound to CENP-ANuc reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-ANuc, and a linker DNA segment of the α-satellite repeat emerges from the fully wrapped end of the nucleosome to thread through the central CENP-LN channel that tightly grips the DNA. The CENP-TWSX histone-fold module further augments DNA binding and partially wraps the linker DNA in a manner reminiscent of canonical nucleosomes. Our study suggests that the topological entrapment of the linker DNA by CCAN provides a robust mechanism by which kinetochores withstand both pushing and pulling forces exerted by the mitotic spindle.

MeSH terms

  • Centromere / chemistry
  • Centromere Protein A* / chemistry
  • Cryoelectron Microscopy
  • DNA / chemistry
  • Humans
  • Kinetochores* / chemistry
  • Nucleosomes* / chemistry
  • Protein Binding


  • Centromere Protein A
  • Nucleosomes
  • DNA