Stepwise unfolding supports a subunit model for vertebrate kinetochores

Giulia Vargiu, Alex Makarov, James Allan, Tatsuo Fukagawa, William Earnshaw*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

During cell division, interactions between microtubules and chromosomes are mediated by the kinetochore, a proteinaceous structure located at the primary constrictionof chromosomes. In addition to the centromere histone CENP-A, other members of the Constitutive Centromere Associated Network (CCAN), participate in the formation of a chromatin-associated scaffold that supports kinetochore structure. We performed a targeted screen analysing unfolded centrochromatin from centromere protein (CENP) depleted chromosomes. Our results revealed that CENP-C and CENP-S are critical for the stable folding of mitotic kinetochore chromatin. Multi‐peak fitting algorithms revealed the presence of an organised pattern of centrochromatin packing consistent with arrangement of CENP‐A containing nucleosomes into up to five chromatin “subunits” – each containing roughly 20‐30 nucleosomes. These subunits could be either layers of a boustrophedon or small loops of centromeric chromatin.
Original languageEnglish
Pages (from-to)3133-3138
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume114
Issue number12
Early online date6 Mar 2017
DOIs
Publication statusPublished - 21 Mar 2017

Keywords

  • Boustrophedon
  • CENP-A
  • Centrochromatin
  • Centromere
  • Kinetochore

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