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A diverse array of interphase chromosomal functions supported by condensins. (A) Condensin II promotes the disassembly of polytene chromosomes in D. melanogaster. (B) Condensin II antagonizes transvection in D. melanogaster, possibly by restricting physical interactions between homologous chromosomes. (C) In C. elegans hermaphrodites , condensin I DC associates with both X chromosomes and down-regulates expression of X-linked genes by half, possibly by changing higher-order chromosome structures of the X. (D) S. cerevisiae condensin plays a crucial role in stabilizing the rDNA repeat. (E) S. cerevisiae condensin promotes clustering (and subsequent nucleolar localization) of tRNA genes that are scattered along its genome.
Source publication
Condensins are multisubunit protein complexes that play a fundamental role in the structural and functional organization of chromosomes in the three domains of life. Most eukaryotic species have two different types of condensin complexes, known as condensins I and II, that fulfill nonoverlapping functions and are subjected to differential regulatio...
Citations
... Condensin I and condensin II, two types of DNA condensin complexes, involve in chromosome condensation and segregation during mitosis in most eukaryotic cells [15]. Non-SMC condensin I complex subunit H (NCAPH), located on chromosome 2q11.2, is an essential regulatory subunit of condensin I [16]. ...
... Non-SMC condensin I complex subunit H (NCAPH), located on chromosome 2q11.2, is an essential regulatory subunit of condensin I [16]. NCAPH maintains the stability of the condensin complex and ensures the precision of sister chromatids separation in cell mitosis [15][16][17]. NCAPH can effectively regulate the mature DNA damage and chromosome condensation [18]. Additionally, NCAPH can possibly affect development of the various tumors. ...
... NCAPH, a subunit of condensin I, plays an important role in the accurate segregation of sister chromatids during the maintenance of mitosis [15][16][17]. NCAPH has been shown to promote the malignant progression of many cancers, such as breast cancer [38], bladder cancer [24], and colorectal cancer [20]. Our study found that NCAPH is highly expressed in gliomas and associated with poor prognosis. ...
Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) has been shown to facilitate progression and predict adverse prognostic outcome in many cancer types. However, the function of NCAPH in gliomas is still unclear. Series of experiments were taken to uncover the function of NCAPH in glioma. The expression of NCAPH and potential mechanism regulating progression of glioma was verified by bioinformatics analysis. Lentiviral transfection was used for establishment of loss-of-function and gain-of-function cell lines. CCK-8 assay and Colony-formation assay were used to evaluate proliferation. Transwell assay and Cell wound healing assay were used to assess migration and invasion. Cell cycle and apoptosis were measured by flow cytometry. Protein and RNA were quantified by WB and RT-PCR, respectively. The nude mice model of glioma was used to evaluate the effect of NCAPH in vivo. The expression of NCAPH increased significantly in glioma tissues and correlated with WHO grade, IDH wild-type and non-1p/19q codeletion. Glioma patients with high expression of NCAPH had an undesirable prognosis. Functionally, upregulated NCAPH promotes the malignant hallmarks of glioma cells in vivo and in vitro. NCAPH correlated with DNA damage repair ability of glioma cells and facilitated the proliferation, invasion, and migration of glioma cells by promoting the PI3K/AKT signaling pathway. This study identifies the important pro-tumor role of NCAPH in glioma and suggests that NCAPH is a potential therapeutic target.
... The observed PfCAP-H expression agrees with the transcriptional profiling data (15), indicating a likely role for PfCAP-H during asexual development. Given that PfCAP-H homologs are present near centrosomes in other organisms (12), we performed an IFA on schizonts with an antibody that recognizes Plasmodium centrins as a marker for the centrosome in these parasites. PfCAP-H localizes near the centrosomes (Fig. 1C), similar to the reported localizations for PbSMC2/4 (14). ...
Condensin I is a pentameric complex that regulates the mitotic chromosome assembly in eukaryotes. The kleisin subunit CAP-H of the condensin I complex acts as a linchpin to maintain the structural integrity and loading of this complex on mitotic chromosomes. This complex is present in all eukaryotes and has recently been identified in Plasmodium spp. However, how this complex is assembled and whether the kleisin subunit is critical for this complex in these parasites are yet to be explored. To examine the role of PfCAP-H during cell division within erythrocytes, we generated an inducible PfCAP-H knockout parasite. We find that PfCAP-H is dynamically expressed during mitosis with the peak expression at the metaphase plate. PfCAP-H interacts with PfCAP-G and is a non-SMC member of the condensin I complex. Notably, the absence of PfCAP-H does not alter the expression of PfCAP-G but affects its localization at the mitotic chromosomes. While mitotic spindle assembly is intact in PfCAP-H-deficient parasites, duplicated centrosomes remain clustered over the mass of unsegmented nuclei with failed karyokinesis. This failure leads to the formation of an abnormal nuclear mass, while cytokinesis occurs normally. Altogether, our data suggest that PfCAP-H plays a crucial role in maintaining the structural integrity of the condensin I complex on the mitotic chromosomes and is essential for the asexual development of malarial parasites.
IMPORTANCE
Mitosis is a fundamental process for Plasmodium parasites, which plays a vital role in their survival within two distinct hosts—human and Anopheles mosquitoes. Despite its great significance, our comprehension of mitosis and its regulation remains limited. In eukaryotes, mitosis is regulated by one of the pivotal complexes known as condensin complexes. The condensin complexes are responsible for chromosome condensation, ensuring the faithful distribution of genetic material to daughter cells. While condensin complexes have recently been identified in Plasmodium spp., our understanding of how this complex is assembled and its precise functions during the blood stage development of Plasmodium falciparum remains largely unexplored. In this study, we investigate the role of a central protein, PfCAP-H, during the blood stage development of P. falciparum. Our findings reveal that PfCAP-H is essential and plays a pivotal role in upholding the structure of condensin I and facilitating karyokinesis.
... Condensins are large protein complexes that assemble interphase chromatin into chromosomes and organise their segregation during mitosis and meiosis. 21 Two condensin complexes have been described, 22 of which the condensin II complex is predominantly located in the nucleus during interphase and binds to chromosomes during mitosis. [23][24][25] Conversely, the condensin I complex is located in the cytoplasm and binds to chromosomes after rupture of the nuclear membrane. ...
Background
Luminal A tumours generally have a favourable prognosis but possess the highest 10‐year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post‐diagnosis. Identifying such patients is crucial as long‐term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment.
Methods
We conducted a study to explore non‐structural chromosome maintenance condensin I complex subunit H’s (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels.
Results
We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)‐ NCAPH ErbB2 double‐transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10‐gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression.
Conclusions
The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.
... Additionally, while condensin II was thought to be absent in fungi 15 , we detected its presence in the fungus Gonapodya prolifera. Considering that condensin II is also found in fungal relatives like the nucleariid Parvularia atlantis, it may still have been present in the last common ancestor of Fungi, and subsequently lost in multiple fungal lineages. ...
Across the tree of life, SMC complexes organize, segregate and regulate DNA. In contrast to prokaryotes, which often possess one SMC complex, eukaryotes usually have four such complexes. This expanded set is involved in managing the considerably larger nuclear genomes of eukaryotes, which are distributed across multiple chromosomes. Despite their essential functions, SMC complexes exhibit variations across model eukaryotes, suggesting an even greater variety of these complexes that remains unexplored. Here, we aimed to uncover the diversity and evolution of SMC complexes across eukaryotes, and their deeper, prokaryotic evolutionary origins. For this, we conducted in-depth comparative genomic and phylogenetic analyses of SMC complexes. We show that the last eukaryotic common ancestor (LECA) likely had fully-fledged versions of all four complexes and that the condensin II complex was later lost at least 30 times in eukaryotes. We report evidence that proteins previously designated as functional analogs in various model organisms (e.g., Sororin, Securin, Nse5 and Nse6) are in fact genuine orthologs. Finally, we traced the prokaryotic origins of these complexes and propose that a single SMC complex duplicated in an early archaeon. Altogether, we provide a comprehensive overview of eukaryotic SMC complex diversity and evolution, both addressing and generating questions about their functioning in ancestral and contemporary organisms.
... Its primary function involves segregation and alignment of chromosomes [10][11][12]. Condensin I and condensin II are distinct forms of condensin protein complexes found in various eukaryotic cells [13], assembling and segregating chromosomes during both mitosis and meiosis [14]. Furthermore, they may assume specific functions in the context of innate immune responses [15][16][17]. ...
... Whereas condensin I is present and plays an essential function in mitosis in all eukaryotic species studied to date, condensin II is absent in some species or is not essential for mitosis in others (Hirano, 2012). Moreover, a recent study reported evidence suggesting that the condensin II subunits have undergone rapid evolution and suffered recurrent FIGURE 6: CAP-D3 has a unique helical structure that is predicted to directly interact with CAP-G2. ...
In vertebrates, two distinct condensin complexes, condensin I and condensin II, cooperate to drive mitotic chromosome assembly. It remains largely unknown how the two complexes differentially contribute to this process at a mechanistic level. We have previously dissected the role of individual subunits of condensin II by introducing recombinant complexes into Xenopus egg extracts. Here we extend these efforts by introducing a modified functional assay using extracts depleted of topoisomerase IIα (topo IIα), which allows us to further elucidate the functional similarities and differences between condensin I and condensin II. The intrinsically disordered C-terminal region of the CAP-D3 subunit (the D3 C-tail) is a major target of Cdk1 phosphorylation, and phosphorylation-deficient mutations in this region impair condensin II functions. We also identify a unique helical structure in CAP-D3 (the D3 HEAT docker) that is predicted to directly interact with CAP-G2. Deletion of the D3 HEAT docker, along with the D3 C-tail, enhances the ability of condensin II to assemble mitotic chromosomes. Taken together, we propose a self-suppression mechanism unique to condensin II that is released by mitotic phosphorylation. Evolutionary implications of our findings are also discussed.
... One of the roles of condensin is establishing and maintaining a 3D chromosome structure within the nucleus (Hirano, 2012). It is widely accepted that the exact position of DNA has an influence on gene expression levels which can be easily tested experimentally by modifying the chromosome 3D structure within the nucleus (Gibcus & Dekker, 2013). ...
Chromosome (SMC) proteins are a large family of ATPases that play important roles in the organization and dynamics of chromatin. They are central regulators of chromosome dynamics and the core component of condensin. DNA elimination during zygotic somatic genome development is a characteristic feature of ciliated protozoa such as Paramecium . This process occurs after meiosis, mitosis, karyogamy, and another mitosis, which result in the formation of a new germline and somatic nuclei. The series of nuclear divisions implies an important role of SMC proteins in Paramecium sexual development. The relationship between DNA elimination and SMC has not yet been described. Here, we applied RNA interference, genome sequencing, mRNA sequencing, immunofluorescence, and mass spectrometry to investigate the roles of SMC components in DNA elimination. Our results show that SMC4-2 is required for genome rearrangement, whereas SMC4-1 is not. Functional diversification of SMC4 in Paramecium led to a formation of two paralogues where SMC4-2 acquired a novel, development-specific function and differs from SMC4-1. Moreover, our study suggests a competitive relationship between these two proteins.
... Condensin is composed of a core ATPase heterodimer, made of the SMC2 and SMC4 proteins, associated with a kleisin and two HEAT-repeat subunits. Most multicellular eukaryotes possess two condensin variants, named condensin I and II, made of a same SMC2/4 core but associated with distinct sets of non-SMC subunits (Ono et al., 2003;Hirano, 2012). Budding and fission yeasts, in contrast, possess a single condensin complex, similar to condensin I. Thereafter, condensin complexes will be collectively referred to as condensin, unless otherwise stated. ...
The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here, we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosome arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.
... Condensin is composed of a core ATPase heterodimer, made of the SMC2 and SMC4 proteins, associated with a kleisin and two HEAT-repeat subunits. Most multicellular eukaryotes possess two condensin variants, named condensin I and II, made of a same SMC2/4 core but associated with distinct sets of non-SMC subunits (Ono et al, 2003 ;Hirano, 2012 ). Budding and fission yeasts, in contrast, possess a single condensin complex, similar to condensin I. Thereafter, condensin complexes will be collectively referred to as condensin, unless otherwise stated. ...
The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome-remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosome arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.
... Condensin is composed of a core ATPase heterodimer, made of the SMC2 and SMC4 proteins, associated with a kleisin and two HEAT-repeat subunits. Most multicellular eukaryotes possess two condensin variants, named condensin I and II, made of a same SMC2/4 core but associated with distinct sets of non-SMC subunits (Ono et al., 2003;Hirano, 2012). Budding and fission yeasts, in contrast, possess a single condensin complex, similar to condensin I. Thereafter, condensin complexes will be collectively referred to as condensin, unless otherwise stated. ...
The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome-remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosomes arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.
