Regulating levels of centromeric histone H3 (CenH3) variant is crucial for genome stability. Interaction of Psh1, an E3 ligase, with the C terminus of Cse4 has been shown to contribute to its proteolysis. Here, we demonstrate a role for ubiquitination of the N terminus of Cse4 in regulating Cse4 proteolysis for faithful chromosome segregation and a role for Doa1 in ubiquitination of Cse4.
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http://dx.doi.org/10.1534/genetics.113.149898 | DOI Listing |
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 PDFStructure
June 2024
Department of Bioscience and Bioengineering, Indian Institute of Technology, Mumbai, India. Electronic address:
The centromere is epigenetically marked by a histone H3 variant-CENP-A. The budding yeast CENP-A called Cse4, consists of an unusually long N-terminus that is known to be involved in kinetochore assembly. Its disordered chaperone, Scm3 is responsible for the centromeric deposition of Cse4 as well as in the maintenance of a segregation-competent kinetochore.
View Article and Find Full Text PDFInt J Mol Sci
August 2020
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.
Centromere integrity underlies an essential framework for precise chromosome segregation and epigenetic inheritance. Although centromeric DNA sequences vary among different organisms, all eukaryotic centromeres comprise a centromere-specific histone H3 variant, centromeric protein A (CENP-A), on which other centromeric proteins assemble into the kinetochore complex. This complex connects chromosomes to mitotic spindle microtubules to ensure accurate partitioning of the genome into daughter cells.
View Article and Find Full Text PDFEMBO J
July 2020
Department of Molecular Genetics, Faculty of Biology, Center of Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
Kinetochores are chromatin-bound multi-protein complexes that allow high-fidelity chromosome segregation during mitosis and meiosis. Kinetochore assembly is exclusively initiated at chromatin containing Cse4/CENP-A nucleosomes. The molecular mechanisms ensuring that subcomplexes assemble efficiently into kinetochores only at centromeres, but not anywhere else, are incompletely understood.
View Article and Find Full Text PDFGenetics
April 2020
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892
Centromeric localization of CENP-A (Cse4 in , CID in flies, CENP-A in humans) is essential for faithful chromosome segregation. Mislocalization of overexpressed CENP-A contributes to aneuploidy in yeast, flies, and humans, and is proposed to promote tumorigenesis in human cancers. Hence, defining molecular mechanisms that promote or prevent mislocalization of CENP-A is an area of active investigation.
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