Mitotic chromosomes are self-entangled and disentangle through a Topoisomerase II-dependent two stage exit from mitosis
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ABSTRACT:
PROVIDER: PRJNA816145 | ENA |
REPOSITORIES: ENA
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Project description:The topological state of chromosomes determines their mechanical properties, dynamics, and function. Recent work indicated that interphase chromosomes are largely free of entanglements. Here, we use Hi-C, polymer simulations and multi-contact 3C, and propose that, in contrast, mitotic chromosomes are self-entangled. We explore how a mitotic self-entangled state is converted into an unentangled interphase state during mitotic exit. Most mitotic entanglements are removed during anaphase/telophase, with remaining ones removed during early G1, in a Topoisomerase II-dependent process. Polymer models suggest a two-stage disentanglement pathway: first, decondensation of mitotic chromosomes with remaining condensin loops produces entropic forces that bias Topoisomerase II activity towards decatenation. At the second stage, the loops are released, and formation of new entanglements is prevented by lower Topoisomerase II activity, allowing the establishment of unentangled and territorial G1 chromosomes. When mitotic entanglements are not removed, in experiment and models, a normal interphase state cannot be acquired.
2024-03-07 | GSE198610 | GEO
Project description:The genome is thought to be transcriptionally silent during mitosis. Technical limitations have prevented the sensitive mapping of mitotic transcription and transcription reactivation during mitotic exit, and thus the networks by which transcriptome dynamics govern the generation of daughter cells have been unclear. We used 5-ethynyluridine to pulse-label intact transcripts during mitosis and mitotic exit and find that the first round of transcription activates genes that are involved in macromolecular synthesis, rather than cell identity. Many interphase genes exhibit residual transcription in mitosis, as confirmed by different methods of assessment, and a subset of genes are more highly transcribed in mitosis than in interphase. We suggest that mitotic transcription may serve an epigenetic function in restoring proper transcription patterns during mitotic exit.
2017-09-20 | GSE87476 | GEO
Project description:By following chromatin occupancy of RNAPII and TOP1 using ChIP-seq throughout mitosis, we found that TOP1 is required for RNAPII translocation along genes. The stimulation of TOP1 activity through its interaction with RNAPII during elongation, allowed RNAPII clearance from genes in prometaphase and enabled proper chromosomal segregation. Interference with the TOP1-RNAPII interaction or acute depletion of TOP1 at the onset of mitosis impaired RNAPII spiking at promoters, which is necessary for the first pioneering round of transcription during mitotic exit, and triggered defects in the transcriptional program of the post-mitotic cells.
2021-11-11 | GSE171132 | GEO
Project description:Candida albicans demonstrates three main growth morphologies yeast, pseudohyphal and true hyphal forms. Cell separation is distinct in these morphological forms and the process of separation is closely linked to the completion of mitosis and cytokinesis. In Saccharomyces cerevisiae the small GTPase Tem1 is known to initiate the mitotic exit network, a signalling pathway involved in signalling the end of mitosis and initiating cytokinesis and cell separation. We have characterised the role of Tem1 in C. albicans, and demonstrate that it is essential for mitotic exit and cytokinesis, and that this essential function is signalled through the kinase Cdc15. Consistent with its role in activating the mitotic exit network Tem1 localised to spindle pole bodies in a cell cycle dependent manner. Cells depleted of Tem1 displayed highly polarised growth but ultimately fail to complete cytokinesis and re-enter the cell cycle following nuclear division. At the transcriptional level genes downregulated following the depletion of Tem1 where significantly enriched for genes whose expression peaks early in the cell cycle and for those associated with glycolysis. For expression analysis triplicate RNA samples were generated from exponentially growing C. albicans yeast cells and from cells following 8 h inhibition of TEM1 expression. Gene expression was determined using RNA-seq on the Illumina HiSeq 2000 platform.
2014-01-01 | E-GEOD-48650 | biostudies-arrayexpress
Project description:Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1
| PRJNA718529 | ENA
Project description:Candida albicans demonstrates three main growth morphologies yeast, pseudohyphal and true hyphal forms. Cell separation is distinct in these morphological forms and the process of separation is closely linked to the completion of mitosis and cytokinesis. In Saccharomyces cerevisiae the small GTPase Tem1 is known to initiate the mitotic exit network, a signalling pathway involved in signalling the end of mitosis and initiating cytokinesis and cell separation. We have characterised the role of Tem1 in C. albicans, and demonstrate that it is essential for mitotic exit and cytokinesis, and that this essential function is signalled through the kinase Cdc15. Consistent with its role in activating the mitotic exit network Tem1 localised to spindle pole bodies in a cell cycle dependent manner. Cells depleted of Tem1 displayed highly polarised growth but ultimately fail to complete cytokinesis and re-enter the cell cycle following nuclear division. At the transcriptional level genes downregulated following the depletion of Tem1 where significantly enriched for genes whose expression peaks early in the cell cycle and for those associated with glycolysis.
2014-01-01 | GSE48650 | GEO
Project description:Entry into mitosis is driven by the coordinated phosphorylation of thousands of proteins. For the cell to complete mitosis and divide into two identical daughter cells it must regulate dephosphorylation of these proteins in a highly ordered, temporal manner. There is currently a lack of a complete understanding of the phosphorylation changes that occur during the initial stages of mitotic exit in human cells. Therefore, we performed a large unbiased, global analysis to map the very first dephosphorylation events that occur as cells exit mitosis. We identified and quantified the modification of >16,000 phosphosites on >3,300 unique proteins during early mitotic exit, providing up to 8-fold greater resolution than previous studies. Only a small fraction (~10%) of phosphorylation sites were dephosphorylated during early mitotic exit and these occurred on proteins involved in critical early exit events, including organization of the mitotic spindle, the spindle assembly checkpoint, and reformation of the nuclear envelope. Surprisingly this enrichment was observed across all kinase consensus motifs, indicating that it is independent of the upstream phosphorylating kinase. Therefore, dephosphorylation of these sites is likely determined by the specificity of phosphatase/s rather than the activity of kinase/s. Dephosphorylation was significantly affected by the amino acids at and surrounding the phosphorylation site, with several unique evolutionarily conserved amino acids correlating strongly with phosphorylation status. These data provide a potential mechanism for the specificity of phosphatases, and how they co-ordinate the ordered events of mitotic exit. In summary, our results provide a global overview of the phosphorylation changes that occur during the very first stages of mitotic exit, providing novel mechanistic insight into how phosphatase/s specifically regulate this critical transition.
2015-06-25 | PXD001559 | Pride
Project description:Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1 [ChIP-seq]
| PRJNA718530 | ENA
Project description:Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1 [SLAM-seq]
| PRJNA718531 | ENA
Project description:The cell division cycle culminates in mitosis when two daughter cells are born. As cyclin-dependent kinase (Cdk) activity reaches its peak, the Anaphase Promoting Complex (APC) is activated to trigger sister chromatid separation and mitotic spindle elongation, followed by spindle disassembly and cytokinesis. Degradation of mitotic cyclins and activation of Cdk-counteracting phosphatases are thought to cause protein dephosphorylation to control these sequential events. Here, we use budding yeast to analyze phosphorylation dynamics of 3456 phosphosites on 1101 proteins with high temporal resolution as cells progress synchronously through mitosis. This illustrates sequential protein dephosphorylation and reveals that the order arises from successive inactivation of S and M phase Cdks and of the mitotic kinase Polo. Unexpectedly, we detect as many new phosphorylation events as there are dephosphorylation events. These correlate with late mitotic kinase activation and identify numerous candidate targets of these kinases. Our findings revise our view of mitotic exit and portray it as a dynamic process in which a range of mitotic kinases instruct the order of both protein dephosphorylation as well as phosphorylation.
2018-10-15 | PXD008327 | Pride