The kinetochore is a key cell division organelle that enables high-fidelity transmission of genetic information by coupling chromosomes to spindle microtubules during mitosis and meiosis. Despite its cytological description more than a century ago, remarkably little information is available on kinetochore function at a molecular level. Recently, important advances elucidating the overall organization of kinetochores, as well as information about the structures and molecular mechanisms of kinetochore function, have been achieved through a detailed analysis of the kinetochores of the budding yeast Saccharomyces cerevisiae. Here we review the current understanding of kinetochore function in budding yeast and draw comparisons to recent findings in other organisms.
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http://dx.doi.org/10.1146/annurev.biochem.76.052705.160607 | DOI Listing |
Reprod Med Biol
January 2025
Laboratory of Animal Reproduction, Graduate School of Agricultural Sciences Yamagata University Tsuruoka Japan.
Purpose: This study aimed to investigate the molecular mechanisms associated with chromosome segregation errors caused by intrinsic oxidative stress during in vitro oocyte maturation (IVM) using oocytes from -deficient (KO) mice.
Methods: Ovulated or in vitro matured cumulus-cells oocyte complexes (COCs) were collected from wild-type (WT) and KO mice and evaluated chromosome alignment, chromosome segregation, meiotic progression, and BUBR1 and REC8 protein expression levels.
Results: In 21% O IVM, the KO had significantly higher frequencies of chromosome misalignment and segregation errors compared to the WT, and they also reached Germinal Vesicle Break Down (GVBD) and M I stages peak earlier and showed a shorter M I stage residence time compared to the WT.
Mol Biol Cell
January 2025
Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
The mitotic spindle is composed of distinct networks of microtubules, including interpolar bundles that can bridge sister kinetochore fibers and bundles that organize the spindle midzone in anaphase. The crosslinking protein PRC1 can mediate such bundling interactions between antiparallel microtubules. PRC1 is a substrate of mitotic kinases including CDK/cyclin-B, suggesting that it can be phosphorylated in metaphase and dephosphorylated in anaphase.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Healthand, Department of Frontiers Science Center for Disease-related Molecular Network, Core Facilities, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address:
NEK2, a serine/threonine protein kinase, is integral to mitotic events such as centrosome duplication and separation, microtubule stabilization, spindle assembly checkpoint, and kinetochore attachment. However, NEK2 overexpression leads to centrosome amplification and chromosomal instability, which are significantly associated with various malignancies, including liver, breast, and non-small cell lung cancer. This overexpression could facilitate tumor development and confer resistance to therapy by promoting aberrant cell division and centrosome amplification.
View Article and Find Full Text PDFJ Cell Biol
February 2025
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
Kinetochores are multiprotein complexes that link chromosomes to microtubules and are essential for chromosome segregation during cell divisions. In this issue, Alves Domingos et al. (https://doi.
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.
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