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Title | Centromeric chromatin clearings demarcate the site of kinetochore formation. |
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Journal, issue, pages | Cell, Vol. 188, Issue 5, Page 1280-1296.e19, Year 2025 |
Publish date | Mar 6, 2025 |
![]() | Kathryn Kixmoeller / Ekaterina V Tarasovetc / Elie Mer / Yi-Wei Chang / Ben E Black / ![]() |
PubMed Abstract | The centromere is the chromosomal locus that recruits the kinetochore, directing faithful propagation of the genome during cell division. Using cryo-ET on human mitotic chromosomes, we reveal a ...The centromere is the chromosomal locus that recruits the kinetochore, directing faithful propagation of the genome during cell division. Using cryo-ET on human mitotic chromosomes, we reveal a distinctive architecture at the centromere: clustered 20- to 25-nm nucleosome-associated complexes within chromatin clearings that delineate them from surrounding chromatin. Centromere components CENP-C and CENP-N are each required for the integrity of the complexes, while CENP-C is also required to maintain the chromatin clearing. We find that CENP-C is required in mitosis, not just for kinetochore assembly, likely reflecting its role in organizing the inner kinetochore during chromosome segregation. We further visualize the scaffold of the fibrous corona, a structure amplified at unattached kinetochores, revealing crescent-shaped parallel arrays of fibrils extending >1 μm. Thus, we reveal how the organization of centromeric chromatin creates a clearing at the site of kinetochore formation as well as the nature of kinetochore amplification mediated by corona fibrils. |
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Methods | EM (tomography) |
Structure data | ![]() EMDB-44860: Kinetochore on isolated human mitotic chromosome ![]() EMDB-44862: Kinetochore on isolated human mitotic chromosome after degradation of CENP-C ![]() EMDB-44863: Kinetochore on isolated human mitotic chromosome after degradation of CENP-N ![]() EMDB-44864: Kinetochore on isolated human mitotic chromosome under conditions of prolonged spindle detachment |
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