Kinetochores are protein complexes on the chromosomes, whose function as linkers between spindle microtubules and chromosomes is crucial for proper cell division. The mechanisms that facilitate kinetochore capture by microtubules are still unclear. In the present study, we combine experiments and theory to explore the mechanisms of kinetochore capture at the onset of meiosis I in fission yeast. We show that kinetochores on homologous chromosomes move together, microtubules are dynamic and pivot around the spindle pole, and the average capture time is 3-4 minutes. Our theory describes paired kinetochores on homologous chromosomes as a single object, as well as angular movement of microtubules and their dynamics. For the experimentally measured parameters, the model reproduces the measured capture kinetics and shows that the paired configuration of kinetochores accelerates capture, whereas microtubule pivoting and dynamics have a smaller contribution. Kinetochore pairing may be a general feature that increases capture efficiency in meiotic cells.
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http://dx.doi.org/10.1038/srep25736 | DOI Listing |
PLoS One
January 2025
Department of Life Science and Medical Bioscience, Laboratory of Cytoskeletal Logistics, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, Japan.
In mammalian epithelial cells, cytoplasmic microtubules are mainly non-centrosomal, through the functions of the minus-end binding proteins CAMSAP2 and CAMSAP3. When cells enter mitosis, cytoplasmic microtubules are reorganized into the spindle composed of both centrosomal and non-centrosomal microtubules. The function of the CAMSAP proteins upon spindle assembly remains unknown, as these do not exhibit evident localization to spindle microtubules.
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.
View Article and Find Full Text PDFAndrology
December 2024
Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
Background: The establishment of kinetochore-microtubule attachment is essential for error-free chromosome alignment and segregation during cell division. Defects in chromosome alignment result in chromosome instability, birth defects, and infertility. Kinesin-7 CENP-E mediates kinetochore-microtubule capture, chromosome alignment, and spindle assembly checkpoint in somatic cells, however, mechanisms of CENP-E in germ cells remain poorly understood.
View Article and Find Full Text PDFCancer Sci
November 2024
Department of Molecular Oncology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan.
Most cancer cells show increased chromosome missegregation, known as chromosomal instability (CIN), which promotes cancer progression and drug resistance. The underlying causes of CIN in cancer cells are not fully understood. Here we found that breast cancer cell lines show a reduced kinetochore localization of ROD, ZW10, and Zwilch, components of the fibrous corona, compared with non-transformed breast epithelial cell lines.
View Article and Find Full Text PDFJ Mol Cell Biol
October 2024
School of Biological Sciences, The University of Hong Kong, Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong, China.
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