The inner centromere is a region on the mitotic chromosome that serves as a platform for mitotic signaling and possesses unique biophysical properties that enable it to withstand relatively large pulling forces that are generated by kinetochores (KTs) during chromosome segregation. The chromosomal passenger complex (CPC) localizes to and is the key regulator of inner centromere organization and function during mitosis. Recently, we demonstrated that in addition to its kinase and histone code-reading activities, the CPC also can undergo liquid-liquid phase separation (LLPS) and proposed that the inner centromere is a membraneless organelle scaffolded by the CPC. In this perspective, we explore mechanisms that can allow the formation and dissolution of this membraneless body. The cell-cycle-regulated spatially defined assembly and disassembly of the CPC condensate at the inner centromere can reveal general principles about how histone modifications control chromatin-bound membraneless organelles. We further explore how the ability of the CPC to undergo LLPS may contribute to the organization and function of the inner centromere during mitosis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10714244 | PMC |
| http://dx.doi.org/10.1016/j.tcb.2020.06.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Centromeric chromatin clearings demarcate the site of kinetochore formation.
Cell
January 2025
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Biochemistry, Biophysics, Chemical Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA; Institute of Structural Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Center for Genome Integrity, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:
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.
View Article and Find Full Text PDFClassification of Breast Cancer Through the Perspective of Cell Identity Models.
Adv Exp Med Biol
January 2025
INSERM, Bergonie Cancer Institute, University of Bordeaux, Bordeaux, France.
The mammary epithelium has an inner luminal layer that contains estrogen receptor (ER)-positive hormone-sensing cells and ER-negative alveolar/secretory cells, and an outer basal layer that contains myoepithelial/stem cells. Most human tumours resemble either hormone-sensing cells or alveolar/secretory cells. The most widely used molecular classification, the Intrinsic classification, assigns hormone-sensing tumours to Luminal A/B and human epidermal growth factor 2-enriched (HER2E)/molecular apocrine (MA)/luminal androgen receptor (LAR)-positive classes, and alveolar/secretory tumours to the Basal-like class.
View Article and Find Full Text PDFOrganization of the chromosomal passenger complex clusters at inner centromeres in mitosis.
Curr Opin Cell Biol
January 2025
Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan; Department of JFCR Cancer Biology, Institute of Science Tokyo, Tokyo, Japan. Electronic address:
Stable transmission of the genome during cell division is crucial for all life forms and is universally achieved by Aurora B-mediated error correction of the kinetochore-microtubule attachments. Aurora B is the enzymatic subunit of the tetrameric protein complex called the chromosomal passenger complex (CPC), and its centromeric enrichment is required for Aurora B to ensure accurate chromosome segregation. How cells enrich the CPC at centromeres is therefore an outstanding question to be elucidated.
View Article and Find Full Text PDFStable centromere association of the yeast histone variant Cse4 requires its essential N-terminal domain.
EMBO J
January 2025
Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Chromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formation in vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomes in vivo.
View Article and Find Full Text PDFProbing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.
bioRxiv
December 2024
Howard Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!