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Accurate cytokinesis is essential for maintaining genomic integrity. Although the GTPase dynamin has been well studied for its role in vesicular trafficking, its function during mitosis remains poorly understood. In this study, we uncover a novel role for the dynamin homolog, DYN-1, in regulating mitotic spindle pole assembly and the spatiotemporal localization of the key mitotic kinase Polo-like kinase 1 (PLK-1). Our studies demonstrate that the depletion of DYN-1 leads to enlarged metaphase spindle poles and elevated levels of centrosome-associated PLK-1. Strikingly, PLK-1 fails to re-localize from centrosomes to the midbody during late mitosis in a subset of DYN-1-depleted embryos, correlating with abnormal PLK-1 localization at the midbody and defective midbody formation. Importantly, this phenotype is likely not due to increased total PLK-1 protein levels, as DNM2 (human homolog of DYN-1) depletion in HeLa cells did not alter total Plk1 abundance. Together, our findings identify DYN-1 as a new regulator of PLK-1 localization during mitosis and suggest that failure to remove PLK-1 from centrosomes may underlie cytokinesis defects that are observed upon DYN-1 depletion.
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http://dx.doi.org/10.1101/2025.07.21.665896 | DOI Listing |
bioRxiv
July 2025
Department of Biology, North Carolina Agricultural and Technical State University, Greensboro, NC 27411.
Accurate cytokinesis is essential for maintaining genomic integrity. Although the GTPase dynamin has been well studied for its role in vesicular trafficking, its function during mitosis remains poorly understood. In this study, we uncover a novel role for the dynamin homolog, DYN-1, in regulating mitotic spindle pole assembly and the spatiotemporal localization of the key mitotic kinase Polo-like kinase 1 (PLK-1).
View Article and Find Full Text PDFMol Omics
January 2025
Manipal Academy of Higher Education (MAHE), Manipal, 576104, Karnataka, India.
Cisplatin-based concurrent chemoradiotherapy (CCRT) is the standard treatment for cervical patients with locally advanced disease. Despite the improved survival rates and prognosis observed in patients undergoing CCRT, over 30-40% do not achieve complete response and are at risk of locoregional recurrence. Targeting crucial molecules that confer resistance may improve the clinical outcomes of the treatment resistant patient cohort.
View Article and Find Full Text PDFCancer Gene Ther
February 2024
Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, 333, Taiwan.
Intrahepatic cholangiocarcinoma (iCCA) is a subtype of CCA and has a high mortality rate and a relatively poor prognosis. However, studies focusing on increased cell motility and loss of epithelial integrity during iCCA progression remain relatively scarce. We collected seven fresh tumor samples from four patients to perform RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) to determine the transcriptome profile and chromatin accessibility of iCCA.
View Article and Find Full Text PDFLife Sci Alliance
November 2023
Center for Membrane and Cell Physiology, School of Medicine, University of Virginia, Charlottesville, VA, USA
In metazoans, Polo-like kinase (PLK1) controls several mitotic events including nuclear envelope breakdown, centrosome maturation, spindle assembly and progression through mitosis. Here we show that a mutation in the mitochondria-localized protein SPD-3 affects mitotic events by inducing elevated levels of PLK-1 in early embryos. SPD-3 mutant embryos contain abnormally positioned mitotic chromosomes, show a delay in anaphase onset and asymmetrically disassemble the nuclear lamina.
View Article and Find Full Text PDFCurr Biol
June 2023
Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Cell and Devel
During mitosis, chromosomes assemble kinetochores to dynamically couple with spindle microtubules. Kinetochores also function as signaling hubs directing mitotic progression by recruiting and controlling the fate of the anaphase promoting complex/cyclosome (APC/C) activator CDC-20. Kinetochores either incorporate CDC-20 into checkpoint complexes that inhibit the APC/C or dephosphorylate CDC-20, which allows it to interact with and activate the APC/C.
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