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The accuracy of cell division requires precise regulation of the cellular machinery governing DNA/genome duplication, ensuring its equal distribution among the daughter cells. The control of the centrosome cycle is crucial for the formation of a bipolar spindle, ensuring error-free segregation of the genome. The cell and centrosome cycles operate in close synchrony along similar principles. Both require a single duplication round in every cell cycle, and both are controlled by the activity of key protein kinases. Nevertheless, our comprehension of the precise cellular mechanisms and critical regulators synchronizing these two cycles remains poorly defined. Here, we present our hypothesis that the spatiotemporal regulation of a dynamic equilibrium of mitotic kinases activities forms a molecular clock that governs the synchronous progression of both the cell and the centrosome cycles.
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http://dx.doi.org/10.1002/bies.202400048 | DOI Listing |
EMBO Mol Med
September 2025
Institute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, National Stem Cell Translational Resource Center & Ministry of Education Stem Cell Resource Center, Frontier Science Center for Stem Cell Research, School of Li
Primary microcephaly, a rare congenital condition characterized by reduced brain size, occurs due to impaired neurogenesis during brain development. Through whole-exome sequencing, we identified compound heterozygous loss-of-function mutations in CENTRIN 3 (CETN3) in a 5-year-old patient with primary microcephaly. As CETN3 has not been previously linked to microcephaly, we investigated its potential function in neurodevelopment in human pluripotent stem cell-derived cerebral organoids.
View Article and Find Full Text PDFClin Breast Cancer
August 2025
Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. Electronic address:
Background: Triple-negative breast cancer (TNBC) carries a substantial risk of recurrence and metastasis, posing significant threats to patients' health and quality of life. Centrosomal protein 55 (CEP55) has been demonstrated to exhibit elevated expression levels in TNBC. However, its molecular regulatory mechanism in TNBC remains unclear.
View Article and Find Full Text PDFHum Pathol
September 2025
Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address:
Renal cell carcinoma (RCC) is a heterogeneous kidney malignancy driven by complex genetic, molecular, and metabolic alterations. Emerging evidence implicates centrosome dysfunction and autophagy dysregulation in RCC initiation, progression, and resistance to therapy. The centrosome plays a critical role in mitotic fidelity, and its dysfunction often leads to chromosomal and genomic instability.
View Article and Find Full Text PDFNat Commun
September 2025
Department of Physiological Chemistry, Graduate School of Pharmaceutical Science, The University of Tokyo, Bunkyo, Tokyo, Japan.
Copy number control of DNA and centrosomes is essential for accurate genetic inheritance. DNA replication and centrosome duplication have been recognized as parallel key events for cell division. Here, we discover that the DNA replication machinery directly regulates the licensing and execution processes of centrosome duplication to prevent centrosome amplification.
View Article and Find Full Text PDFPLoS Genet
September 2025
Biology of Centrosomes and Genetic Instability Lab, Institut Curie, PSL Research University, CNRS UMR 144, Paris, France.
Unscheduled whole genome duplication (WGD), also described as unscheduled or non-physiological polyploidy, can lead to genetic instability and is commonly observed in human cancers. WGD generates DNA damage due to scaling defects between replication factors and DNA content. As a result DNA damage repair mechanisms are thought to be critical for ensuring cell viability and proliferation under these conditions.
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