Architecture and function of holocentric CENP-A–independent inner kinetochores

Abstract

Kinetochores are essential macromolecular complexes anchoring chromosomes to the mitotic spindle, ensuring faithful cell division. Despite their critical role, the structural organization of kinetochores across diverse species remains poorly understood. We present the inner kinetochore constitutive centromere-associated network (CCAN) structure of the silkmoth Bombyx mori , an insect that lacks the canonical centromere-specifying histone variant CENP-A and exhibits chromosome-wide centromeric activity (holocentric). The B. mori CCAN incorporates four previously uncharacterized centromeric subunit proteins that are structurally related to the Dam1/DASH complex but function in scaffolding the inner kinetochore rather than in microtubule binding. Similar to the yeast and human systems, the B. mori CCAN also entraps DNA within its central closed chamber. However, unlike these systems, the B. mori CCAN can also assemble in vitro into a self-contained head-to-head dimer via atypical histone-fold protein dimerization. On the basis of our findings, we propose that the holocentric organization may emerge from the modular arrangement of discrete kinetochore units.

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BibTeX RIS

BibTeX

@article{yu2026architecture,
  title = {{Architecture and function of holocentric CENP-A–independent inner kinetochores}},
  author = {Christine Yu and Sundar Ram Sankaranarayanan and Gaetan Cornilleau and Anna Howes and Caleigh Azumaya and Eric Day and Inna Zilberleyb and Bobby Brillantes and Tommy Cheung and Leonie Dec and Damarys Loew and Phong Tran and Christopher Rose and Ines Anna Drinnenberg and Claudio Ciferri and Stanislau Yatskevich},
  journal = {Science Advances},
  year = {2026},
  month = jun,
  doi = {10.1126/sciadv.aeb5817},
  url = {https://hal.science/hal-05782917v1},
  note = {CC BY-NC},
}

RIS

TY  - JOUR
TI  - Architecture and function of holocentric CENP-A–independent inner kinetochores
AU  - Christine Yu
AU  - Sundar Ram Sankaranarayanan
AU  - Gaetan Cornilleau
AU  - Anna Howes
AU  - Caleigh Azumaya
AU  - Eric Day
AU  - Inna Zilberleyb
AU  - Bobby Brillantes
AU  - Tommy Cheung
AU  - Leonie Dec
AU  - Damarys Loew
AU  - Phong Tran
AU  - Christopher Rose
AU  - Ines Anna Drinnenberg
AU  - Claudio Ciferri
AU  - Stanislau Yatskevich
PY  - 2026
DA  - 2026/06/19
JO  - Science Advances
DO  - 10.1126/sciadv.aeb5817
UR  - https://hal.science/hal-05782917v1
AB  - Kinetochores are essential macromolecular complexes anchoring chromosomes to the mitotic spindle, ensuring faithful cell division. Despite their critical role, the structural organization of kinetochores across diverse species remains poorly understood. We present the inner kinetochore constitutive centromere-associated network (CCAN) structure of the silkmoth Bombyx mori , an insect that lacks the canonical centromere-specifying histone variant CENP-A and exhibits chromosome-wide centromeric activity (holocentric). The B. mori CCAN incorporates four previously uncharacterized centromeric subunit proteins that are structurally related to the Dam1/DASH complex but function in scaffolding the inner kinetochore rather than in microtubule binding. Similar to the yeast and human systems, the B. mori CCAN also entraps DNA within its central closed chamber. However, unlike these systems, the B. mori CCAN can also assemble in vitro into a self-contained head-to-head dimer via atypical histone-fold protein dimerization. On the basis of our findings, we propose that the holocentric organization may emerge from the modular arrangement of discrete kinetochore units.
SN  - 2375-2548
ER  -

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