Journal: Sci Adv / Year: 2026 Title: Architecture and function of holocentric CENP-A-independent inner kinetochores. Authors: Christine Yu / Sundar Ram Sankaranarayanan / Gaetan Cornilleau / Anna C Howes / Caleigh M Azumaya / Eric S Day / Inna Zilberleyb / Bobby Brillantes / Tommy K Cheung / Leonie Dec / Damarys ...Authors: Christine Yu / Sundar Ram Sankaranarayanan / Gaetan Cornilleau / Anna C Howes / Caleigh M Azumaya / Eric S Day / Inna Zilberleyb / Bobby Brillantes / Tommy K Cheung / Leonie Dec / Damarys Loew / Phong Tran / Christopher M Rose / Ines Anna Drinnenberg / Claudio Ciferri / Stanislau Yatskevich / 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 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 , an insect that lacks the canonical centromere-specifying histone variant CENP-A and exhibits chromosome-wide centromeric activity (holocentric). The 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 CCAN also entraps DNA within its central closed chamber. However, unlike these systems, the 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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