The assembly of the mitotic centromere has been extensively studied in recent years, revealing the sequence and regulation of protein loading to this chromosome domain. However, few studies have analyzed centromere assembly during mammalian meiosis. This study specifically targets this approach on mouse spermatocytes. We have found that during prophase I, the proteins of the chromosomal passenger complex Borealin, INCENP, and Aurora-B load sequentially to the inner centromere before Shugoshin 2 and MCAK. The last proteins to be assembled are the outer kinetochore proteins BubR1 and CENP-E. All these proteins are not detected at the centromere during anaphase/telophase I and are then reloaded during interkinesis. The loading sequence of the analyzed proteins is similar during prophase I and interkinesis. These findings demonstrate that the interkinesis stage, regularly overlooked, is essential for centromere and kinetochore maturation and reorganization previous to the second meiotic division. We also demonstrate that Shugoshin 2 is necessary for the loading of MCAK at the inner centromere, but is dispensable for the loading of the outer kinetochore proteins BubR1 and CENP-E.
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http://dx.doi.org/10.1371/journal.pgen.1000417 | DOI Listing |
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 PDFAdv 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 PDFCurr 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 PDFEMBO 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 PDFbioRxiv
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.
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