Hsiao-Tang Hu, Ueh-Ting Tim Wang, Bi-Chang Chen, Yi-Ping Hsueh, Ting-Fang Wang
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引用次数: 0
Abstract
Nuclear lipids play roles in regulatory processes such as signaling, transcriptional regulation, and DNA repair. In this report, we demonstrate that nuclear lipids may contribute to Ki-67-regulated chromosome integrity during mitosis. In COS-7 cells, nuclear lipids are enriched at the perichromosomal layer and excluded from intrachromosomal regions during early mitosis, but are then detected in intrachromosomal regions during late mitosis, as revealed by TT-ExM, an improved expansion microscopy technique that enables high-sensitivity, super-resolution imaging of proteins, lipids, and nuclear DNA. The nuclear non-histone protein Ki-67 acts as a surfactant to form a repulsive molecular brush around fully condensed sister chromatids in early mitosis, preventing the diffusion or penetration of nuclear lipids into intrachromosomal regions. Ki-67 is phosphorylated during mitosis by cyclin-dependent kinase 1 (CDK1), the best-known master regulator of the cell cycle. Both Ki-67 knockdown and reduced Ki-67 phosphorylation by CDK1 inhibitors allow nuclear lipids to penetrate chromosomal regions. Thus, both Ki-67 protein level and phosphorylation status during mitosis appear to influence the perichromosomal distribution of nuclear lipids. Ki-67 knockdown and CDK1 inhibition also lead to uneven chromosome disjunction between daughter cells, highlighting the critical role of this regulatory mechanism in ensuring accurate chromosome segregation. Given that Ki-67 has been proposed to promote chromosome individualization and establish chromosome-cytoplasmic compartmentalization during open mitosis in vertebrates, our results reveal that nuclear lipid enrichment at the perichromosomal layer enhances Ki-67's ability to form a protective perichromosomal barrier (chromosome envelope), which is critical for correct chromosome segregation and maintenance of genome integrity during mitosis.
期刊介绍:
The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.