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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 over large centromeric regions and across diverse species remains poorly understood. We present the inner kinetochore (CCAN) structure of the silkmoth Bombyx mori, an insect without the canonical centromeric CENP-A gene and with chromosome-wide centromeric activity (holocentric). Our analyses reveal a ring-shaped complex with structural parallels to the known human and yeast kinetochores. Notably, B. mori CCAN incorporates four previously uncharacterized proteins, Centromeric Subunits 1-4, which have unexpected evolutionary relationships to the outer kinetochore Dam1/DASH complex. We demonstrate that CCAN binds DNA as a distinctive head-to-head dimer, folding the DNA into a loop and generating an alternative point-centromere-like architecture poised for chromosome segregation. Our work establishes this self-contained CCAN dimer as a key structural unit that forms the basis of a holocentric organization and suggests that large-scale centromere architectures can emerge from the modular arrangement of such discrete kinetochore units.

INSTRUMENT(S):

ORGANISM(S): Spodoptera Frugiperda

TISSUE(S): Cell Culture

SUBMITTER: Vanessa Masson

LAB HEAD: Damarys Loew

PROVIDER: PXD063391 | Pride | 2026-04-20

REPOSITORIES: Pride

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			Action	DRS
	20240523_143909_Ines_Drinnenberg_Quanti_07052024.sne	Other
	DesignPRIDE.xlsx	Xlsx
	X8722LD.raw	Raw
	X8723LD.raw	Raw
	X8724LD.raw	Raw

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