Ki-67 and CDK1 control the dynamic association of nuclear lipids with mitotic chromosomes
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 perichromosom...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524002360 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832582211555033088 |
|---|---|
| author | Hsiao-Tang Hu Ueh-Ting Tim Wang Bi-Chang Chen Yi-Ping Hsueh Ting-Fang Wang |
| author_facet | Hsiao-Tang Hu Ueh-Ting Tim Wang Bi-Chang Chen Yi-Ping Hsueh Ting-Fang Wang |
| author_sort | Hsiao-Tang Hu |
| collection | DOAJ |
| description | 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 (expansion microscopy with trypsin digestion and tyramide signal amplification), an improved expansion microscopy technique that enables high-sensitivity and super-resolution imaging of proteins, lipids, and nuclear DNA. The nuclear nonhistone 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 the ability of Ki-67 to form a protective perichromosomal barrier (chromosome envelope), which is critical for correct chromosome segregation and maintenance of genome integrity during mitosis. |
| format | Article |
| id | doaj-art-0b0627e9059a458ebe1efb445b7bf801 |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-0b0627e9059a458ebe1efb445b7bf8012025-01-30T05:12:42ZengElsevierJournal of Lipid Research0022-22752025-01-01661100731Ki-67 and CDK1 control the dynamic association of nuclear lipids with mitotic chromosomesHsiao-Tang Hu0Ueh-Ting Tim Wang1Bi-Chang Chen2Yi-Ping Hsueh3Ting-Fang Wang4Institute of Molecular Biology, Academia Sinica, Taipei, TaiwanResearch Center for Applied Sciences, Academia Sinica, Taipei, Taiwan; Department of Photonics, National Yang Ming Chiao Tung University, Hsinchu, TaiwanResearch Center for Applied Sciences, Academia Sinica, Taipei, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan; For correspondence: Ting-Fang Wang; Yi-Ping HsuehInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan; For correspondence: Ting-Fang Wang; Yi-Ping HsuehNuclear 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 (expansion microscopy with trypsin digestion and tyramide signal amplification), an improved expansion microscopy technique that enables high-sensitivity and super-resolution imaging of proteins, lipids, and nuclear DNA. The nuclear nonhistone 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 the ability of Ki-67 to form a protective perichromosomal barrier (chromosome envelope), which is critical for correct chromosome segregation and maintenance of genome integrity during mitosis.http://www.sciencedirect.com/science/article/pii/S0022227524002360biotin-DHPEcell cyclecell cycle-dependent kinase 1expansion microscopyKi-67nuclear lipid |
| spellingShingle | Hsiao-Tang Hu Ueh-Ting Tim Wang Bi-Chang Chen Yi-Ping Hsueh Ting-Fang Wang Ki-67 and CDK1 control the dynamic association of nuclear lipids with mitotic chromosomes Journal of Lipid Research biotin-DHPE cell cycle cell cycle-dependent kinase 1 expansion microscopy Ki-67 nuclear lipid |
| title | Ki-67 and CDK1 control the dynamic association of nuclear lipids with mitotic chromosomes |
| title_full | Ki-67 and CDK1 control the dynamic association of nuclear lipids with mitotic chromosomes |
| title_fullStr | Ki-67 and CDK1 control the dynamic association of nuclear lipids with mitotic chromosomes |
| title_full_unstemmed | Ki-67 and CDK1 control the dynamic association of nuclear lipids with mitotic chromosomes |
| title_short | Ki-67 and CDK1 control the dynamic association of nuclear lipids with mitotic chromosomes |
| title_sort | ki 67 and cdk1 control the dynamic association of nuclear lipids with mitotic chromosomes |
| topic | biotin-DHPE cell cycle cell cycle-dependent kinase 1 expansion microscopy Ki-67 nuclear lipid |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524002360 |
| work_keys_str_mv | AT hsiaotanghu ki67andcdk1controlthedynamicassociationofnuclearlipidswithmitoticchromosomes AT uehtingtimwang ki67andcdk1controlthedynamicassociationofnuclearlipidswithmitoticchromosomes AT bichangchen ki67andcdk1controlthedynamicassociationofnuclearlipidswithmitoticchromosomes AT yipinghsueh ki67andcdk1controlthedynamicassociationofnuclearlipidswithmitoticchromosomes AT tingfangwang ki67andcdk1controlthedynamicassociationofnuclearlipidswithmitoticchromosomes |