Cohesin is essential for the timely activation of condensin and anaphase segregation
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE203117 | GEO | 2025/09/01
REPOSITORIES: GEO
Similar Datasets
Project description:Chromosome segregation requires both the separation of sister chromatids and the sustained condensation of chromatids during anaphase. In yeast cells, cohesin is not only required for sister chromatid cohesion but also plays a major role in determining the structure of individual chromatids in metaphase. Separase cleavage is thought to remove all cohesin complexes from chromosomes to initiate anaphase. It is thus not clear how the length and organisation of segregating chromatids are maintained during anaphase in the absence of cohesin. Here we show that degradation of cohesin at the anaphase onset causes aberrant chromatid segregation. Hi-C analysis on segregating chromatids demonstrates that cohesin depletion causes loss of intrachromatid organisation. Surprisingly, TEV-mediated cleavage of cohesin does not dramatically disrupt chromatid organisation in anaphase, explaining why bulk segregation is achieved. In addition, we identified a small pool of cohesin complexes bound to telophase chromosomes in wildtype cells and show that they play a role in the organisation of centromeric regions. Our data demonstrate that in yeast cells, cohesin function is not over in metaphase, but extends to the anaphase period when chromatids are segregating.
2022-10-01 | GSE183481 | GEO
Project description:FACT mediates cohesin function on chromatin Cohesin is a key regulator of genome architecture with roles in sister chromatid cohesion and the organisation of higher-order structures during interphase and mitosis. The recruitment and mobility of cohesin complexes on DNA are restricted by nucleosomes. Here we show that cohesin role in chromosome organization requires the histone chaperone FACT. Depletion of FACT in metaphase cells affects cohesin stability on chromatin reducing its accumulation at pericentric regions and binding on chromosome arms. Using Hi-C, we show that cohesin-dependent TAD (Topological Associated Domains)-like structures in G1 and metaphase chromosomes are disrupted in the absence of FACT. Surprisingly, sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our results uncover a role for FACT in genome organisation by facilitating cohesin dependent compartmentalization of chromosomes into loop domains.
2019-10-03 | PXD014896 | Pride
Project description:The chromosomal condensin complex gives metaphase chromosomes structural stability. In addition, condensin is required for sister chromatid resolution during their segregation in anaphase. How condensin promotes chromosome resolution is poorly understood. Chromosome segregation during anaphase also fails after inactivation of topoisomerase II (topo II), the enzyme that removes catenation between sister chromatids left behind after completion of DNA replication. This has led to the proposal that condensin promotes DNA decatenation, but direct evidence for this is missing and alternative roles for condensin in chromosome resolution have been suggested. Using the budding yeast rDNA as a model, we now show that anaphase bridges in a condensin mutant are resolved by ectopic expression of a foreign (Chlorella virus) but not endogenous topo II. This suggests that catenation prevents sister rDNA segregation, and that yeast topo II is ineffective in decatenating the locus without condensin. Condensin and topo II colocalize along both rDNA and euchromatin, consistent with coordination of their activities. We investigate the physiological consequences of condensin-dependent rDNA decatenation and find that late decatenation determines the late segregation timing of this locus during anaphase. Regulation of decatenation therefore provides a means to finetune segregation timing of chromosomes in mitosis. Keywords: ChIP-chip, Cell Cycle
2008-07-18 | GSE11988 | GEO
Project description:The dramatic change in morphology of chromosomal DNAs between interphase and mitosis is one of the defining features of the eukaryotic cell cycle. Two types of enzymes, namely cohesin and condensin confer the topology of chromosomal DNA by extruding DNA loops. While condensin normally configures chromosomes exclusively during mitosis, cohesin does so during interphase. The processivity of cohesin’s loop extrusion during interphase is limited by a regulatory factor called WAPL, which induces cohesin to dissociate from chromosomes via a mechanism that requires dissociation of its kleisin from the neck of SMC3. We show here that a related mechanism may be responsible for blocking condensin II from acting during interphase. Cells derived from patients affected by microcephaly caused by mutations in the MCPH1 gene undergo premature chromosome condensation but it has never been established for certain whether MCPH1 regulates condensin II directly. We show that deletion of Mcph1 in mouse embryonic stem cells unleashes an activity of condensin II that triggers formation of compact chromosomes in G1 and G2 phases, which is accompanied by enhanced mixing of A and B chromatin compartments, and that this occurs even in the absence of CDK1 activity. Crucially, inhibition of condensin II by MCPH1 depends on the binding of a short linear motif within MCPH1 to condensin II’s NCAPG2 subunit. We show that the activities of both Cohesin and Condensin II may be restricted during interphase by similar types of mechanisms as MCPH1’s ability to block condensin II’s association with chromatin is abrogated by the fusion of SMC2 with NCAPH2. Remarkably, in the absence of both WAPL and MCPH1, cohesin and condensin II transform chromosomal DNAs of G2 cells into chromosomes with a solenoidal axis showing that both cohesin and condensin must be tightly regulated to adjust the structure of chromatids for their successful segregation.
2021-11-19 | GSE188988 | GEO
Project description:SMC proteins are essential components of three protein complexes that are important for chromosome structure and function. The cohesin complex holds replicated sister chromatids together, whereas the condensin complex has an essential role in mitotic chromosome architecture. Both are involved in interphase genome organisation. SMC-containing complexes are large (>650 kDa for condensin) and contain long anti-parallel coiled-coils. They are thus difficult subjects for conventional crystallographic and electron cryomicroscopic studies. Here we have used amino acid-selective cross-linking and mass spectrometry (CLMS) combined with structure prediction to develop a full-length molecular draft 3D-structure of the SMC2/SMC4 dimeric backbone of chicken condensin. We assembled homology-based molecular models of the globular heads and hinges with the lengthy coiled-coils modelled in fragments, using numerous high-confidence cross-links and accounting for potential irregularity. Our experiments reveal that isolated condensin complexes can exist with their coiled-coil segments closely apposed to one another along their lengths and define the relative spatial alignment of the two anti-parallel coils. The centres of the coiled-coils can also approach one another closely in situ in mitotic chromosomes. In addition to revealing structural information, our cross-linking data suggest that both H2A and H4 may have roles in condensin interactions with chromatin.
2015-07-13 | PXD001835 | Pride
Project description:Structural Maintenance of chromosomes (SMC) complexes, cohesin and condensins, have been named after their roles during meiosis and mitosis. Recent data in mammalian cells and Drosophila have described the additional role of cohesin for genome folding into loops and domains during interphase. However, determinants of genome folding in holocentric species remain unclear. Using high resolution chromosome conformation capture, we show that overlapping large-scale nuclear localization and small-scale epigenomic states compartmentalize the C. elegans genome. By systematically and acutely inactivating each SMC complex, we observe that in contrast to other studied systems, cohesin creates small loops, while condensin I has a major role in genome folding: its inactivation causes genome-wide decompaction, chromosome mixing, loss of loops and TAD structures and reinforcement of fine-scale epigenomic compartments. Counter-intuitively, removal of condensin I and its X-specific variant condensin IDC from the X chromosomes led to the formation of a loop compartment coinciding with a subset of previously characterized loading sites for condensin IDC and bound by the X-targeting complex SDC. While transcriptional changes were limited for all autosomes upon cohesin and condensin II inactivation, removal of condensin I/IDC from the X chromosome led to transcriptional up-regulation of X-linked genes demonstrating that a sustained role for condensin IDC in gene regulation. Finally, while condensin I inactivation leads to reduced lifespan, we show that this reduction is due to X-specific gene upregulation rather than global genome decompaction.
2024-04-18 | GSE199721 | GEO
Project description:Structural Maintenance of chromosomes (SMC) complexes, cohesin and condensins, have been named after their roles during meiosis and mitosis. Recent data in mammalian cells and Drosophila have described the additional role of cohesin for genome folding into loops and domains during interphase. However, determinants of genome folding in holocentric species remain unclear. Using high resolution chromosome conformation capture, we show that overlapping large-scale nuclear localization and small-scale epigenomic states compartmentalize the C. elegans genome. By systematically and acutely inactivating each SMC complex, we observe that in contrast to other studied systems, cohesin creates small loops, while condensin I has a major role in genome folding: its inactivation causes genome-wide decompaction, chromosome mixing, loss of loops and TAD structures and reinforcement of fine-scale epigenomic compartments. Counter-intuitively, removal of condensin I and its X-specific variant condensin IDC from the X chromosomes led to the formation of a loop compartment coinciding with a subset of previously characterized loading sites for condensin IDC and bound by the X-targeting complex SDC. While transcriptional changes were limited for all autosomes upon cohesin and condensin II inactivation, removal of condensin I/IDC from the X chromosome led to transcriptional up-regulation of X-linked genes demonstrating that a sustained role for condensin IDC in gene regulation. Finally, while condensin I inactivation leads to reduced lifespan, we show that this reduction is due to X-specific gene upregulation rather than global genome decompaction.
2024-04-18 | GSE199719 | GEO
Project description:Structural Maintenance of chromosomes (SMC) complexes, cohesin and condensins, have been named after their roles during meiosis and mitosis. Recent data in mammalian cells and Drosophila have described the additional role of cohesin for genome folding into loops and domains during interphase. However, determinants of genome folding in holocentric species remain unclear. Using high resolution chromosome conformation capture, we show that overlapping large-scale nuclear localization and small-scale epigenomic states compartmentalize the C. elegans genome. By systematically and acutely inactivating each SMC complex, we observe that in contrast to other studied systems, cohesin creates small loops, while condensin I has a major role in genome folding: its inactivation causes genome-wide decompaction, chromosome mixing, loss of loops and TAD structures and reinforcement of fine-scale epigenomic compartments. Counter-intuitively, removal of condensin I and its X-specific variant condensin IDC from the X chromosomes led to the formation of a loop compartment coinciding with a subset of previously characterized loading sites for condensin IDC and bound by the X-targeting complex SDC. While transcriptional changes were limited for all autosomes upon cohesin and condensin II inactivation, removal of condensin I/IDC from the X chromosome led to transcriptional up-regulation of X-linked genes demonstrating that a sustained role for condensin IDC in gene regulation. Finally, while condensin I inactivation leads to reduced lifespan, we show that this reduction is due to X-specific gene upregulation rather than global genome decompaction.
2024-04-18 | GSE199717 | GEO
Project description:Structural maintenance of chromosomes (SMC) complexes play critical roles in chromosome dynamics in virtually all organisms but how they function remains poorly understood. In Bacillus subtilis, SMC condensin complexes are topologically loaded at centromeric sites adjacent to the replication origin. Here we provide evidence that these ring-shaped assemblies tether the left and right chromosome arms together while traveling from the origin to the terminus (>2 Mb) at rates >50kb/min. Condensin movement scales linearly with time arguing for an active transport mechanism. These data support a model in which SMC complexes function by processively enlarging DNA loops. Loop formation followed by processive enlargement provides a mechanism for how condensin complexes compact and resolve sister chromatids in mitosis and how cohesin generates topologically associating domains (TADs) during interphase.
2017-02-03 | GSE85612 | GEO
Project description:The duplication and segregation of chromosomes involve the dynamic re-organization of their internal structure by conserved architectural proteins, such as structural maintenance of chromosomes complexes (i.e., cohesin and condensin). Although the roles of these factors is actively investigated, a genome-wide view of chromosome dynamic architecture at both small and large-scales during cell division remains elusive. Here we report the first comprehensive 4D analysis of the Saccharomyces cerevisiae genome higher-order organization during the cell cycle, and investigate the roles of SMC in the observed structural transitions. During replication, cohesion establishment promotes long-range intra-chromosomal contacts and correlates with the individualization of chromosomes, which culminates at metaphase. Mitotic chromosomes are then abruptly reorganized in anaphase by mechanical forces exerted by the mitotic spindle. The formation of a condensin-dependent loop, that bridges the centromere cluster with the rDNA loci, suggests that condensin-mediated forces may also directly facilitate segregation. This work provides a comprehensive overview of chromosome dynamics during the cell cycle of a unicellular eukaryote that recapitulates and unveils new features of highly conserved stages of the cell division.
2017-07-20 | GSE90902 | GEO