Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The CENP-A nucleosome is a key structure for kinetochore assembly. Once the CENP-A nucleosome is established in the centromere, additional proteins recognize the CENP-A nucleosome to form a kinetochore. CENP-C and CENP-N are CENP-A binding proteins. We previously demonstrated that vertebrate CENP-C binding to the CENP-A nucleosome is regulated by CDK1-mediated CENP-C phosphorylation. However, it is still unknown how the phosphorylation of CENP-C regulates its binding to CENP-A. It is also not completely understood how and whether CENP-C and CENP-N act together on the CENP-A nucleosome. Here, using cryo-electron microscopy (cryo-EM) in combination with biochemical approaches, we reveal a stable CENP-A nucleosome-binding mode of CENP-C through unique regions. The chicken CENP-C structure bound to the CENP-A nucleosome is stabilized by an intramolecular link through the phosphorylated CENP-C residue. The stable CENP-A-CENP-C complex excludes CENP-N from the CENP-A nucleosome. These findings provide mechanistic insights into the dynamic kinetochore assembly regulated by CDK1-mediated CENP-C phosphorylation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917552 | PMC |
| http://dx.doi.org/10.15252/embj.2020105671 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Regulation of M18BP1 centromeric localization and CENP-A assembly.
bioRxiv
July 2025
Department of Biochemistry, Stanford University School of Medicine.
Eukaryotic chromosome segregation requires attachment of chromosomes to microtubules of the mitotic spindle through the kinetochore so that chromosomes can align and move in mitosis. Kinetochores are assembled on the centromere which is a unique chromatin domain that is epigenetically defined by the histone H3 variant CENtromere Protein A (CENP-A). During DNA replication CENP-A is equally divided between replicated chromatids and new CENP-A nucleosomes are re-assembled during the subsequent G1 phase of the cell cycle.
View Article and Find Full Text PDFCohesin-mediated stabilization of the CCAN complex at kinetochores in mitosis.
Curr Biol
August 2025
Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD 20892, USA. Electronic address:
The constitutive centromere-associated network (CCAN) of the inner kinetochore links CENP-A-containing nucleosomes of the centromere to the outer kinetochore, ensuring accurate chromosome segregation during mitosis. CCAN binding at the centromere is stabilized upon mitotic entry, but the underlying mechanisms remain unclear. Here, we demonstrate that cohesin is essential for CCAN stability.
View Article and Find Full Text PDFA brief historical perspective on cell cycle control of CENP-A assembly and inheritance.
Chromosome Res
July 2025
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
Centromeres provide the chromosomal scaffold for the assembly of the kinetochore complex, thereby linking replicated sister chromatids to the mitotic spindle, driving their segregation into nascent daughter cells. The location and maintenance of centromeres rely, in large part, on a unique conserved chromatin domain, defined by nucleosomes containing the histone H3 variant, Centromere Protein A (CENP-A), whose discovery 40 years ago we now celebrate. Current models place CENP-A, along with many of its orthologs, at the centre of a self-propagating epigenetic feedback loop that heritably maintains centromere position through mitotic and meiotic divisions.
View Article and Find Full Text PDFCentromeres are essential chromosomal components that ensure proper cell division by serving as assembly sites for kinetochores, which connect chromosomes to spindle microtubules. Centromeres are marked by the evolutionarily conserved centromere-specific histone H3 variant, CENP-A, which is deposited into centromere nucleosomes during G1 in human cells. Centromeres retain cohesin, a ring-like protein complex during mitosis, protecting sister chromatid cohesion and centromere transcription to prevent chromosome missegregation.
View Article and Find Full Text PDFCentromere regulation in the germline and early embryo.
Curr Opin Genet Dev
October 2025
Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA; Penn Center for Genome Integrity, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:
Centromeres are essential for genome inheritance, serving as sites for kinetochore assembly and for final sister chromatid cohesion to ensure accurate chromosome segregation during cell division. These roles must persist through radical physical changes to chromosomes and other biological challenges presented by specialized processes in the germlines of both sexes and during early embryonic development. Centromeres in most organisms are epigenetically defined by the presence of a histone H3 variant, CENP-A.
View Article and Find Full Text PDF