National Institutes of Health/National Cancer Institute (NIH/NCI)
261198
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
134020
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
130302
米国
David and Lucile Packard Foundation
2019-69645
米国
Burroughs Wellcome Fund
1022785
米国
引用
ジャーナル: Cell / 年: 2025 タイトル: Centromeric chromatin clearings demarcate the site of kinetochore formation. 著者: Kathryn Kixmoeller / Ekaterina V Tarasovetc / Elie Mer / Yi-Wei Chang / Ben E Black / 要旨: 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.