Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2025-06-04DOI: 10.1080/19491034.2025.2510106
Kevin N Baumann, Eva Bertosin, Anders Barth, Cees Dekker, Roderick Y H Lim
{"title":"Elucidating the nanoscopic organization and dynamics of the nuclear pore complex.","authors":"Kevin N Baumann, Eva Bertosin, Anders Barth, Cees Dekker, Roderick Y H Lim","doi":"10.1080/19491034.2025.2510106","DOIUrl":"10.1080/19491034.2025.2510106","url":null,"abstract":"<p><p>Due to its pivotal role as a regulator of nucleocytoplasmic transport, the structure and dynamic gating mechanism of the nuclear pore complex (NPC) is a subject of immense interest. Here, we report key recent advancements discussed at the <i>Selective Transport Control in Biological and Biomimetic Nanopores</i> meeting (Monte Verità, Switzerland, 2024) that gathered NPC experts from a range of disciplines. Novel insights were reported from cutting-edge super-resolution techniques that enable the direct interrogation of the NPC's dynamic central transporter; computational models that unravel the mechanisms of the selective barrier; and synthetic NPC mimics as valuable <i>in vitro</i> models for delineating NPC permeability and transport dynamics. Altogether, three major insights were highlighted: (i) the presence of dynamically organised nuclear transport pathways within the NPC, (ii) the role of nuclear transport receptors that enrich and reinforce the NPC's selective permeability barrier, and (iii) the ability of DNA origami nanostructures to mimic aspects of the NPC with unprecedented precision. Overall, the advancements marked a convergence in our understanding of NPC function by unraveling its dynamic gating mechanism at the nanoscale.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2510106"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2025-01-19DOI: 10.1080/19491034.2025.2453752
Tung D Nguyen, Michael A Winek, Mihir K Rao, Shaiva P Dhyani, Monica Y Lee
{"title":"Nuclear envelope components in vascular mechanotransduction: emerging roles in vascular health and disease.","authors":"Tung D Nguyen, Michael A Winek, Mihir K Rao, Shaiva P Dhyani, Monica Y Lee","doi":"10.1080/19491034.2025.2453752","DOIUrl":"10.1080/19491034.2025.2453752","url":null,"abstract":"<p><p>The vascular network, uniquely sensitive to mechanical changes, translates biophysical forces into biochemical signals for vessel function. This process relies on the cell's architectural integrity, enabling uniform responses to physical stimuli. Recently, the nuclear envelope (NE) has emerged as a key regulator of vascular cell function. Studies implicate nucleoskeletal elements (<i>e.g.</i> nuclear lamina) and the linker of nucleoskeleton and cytoskeleton (LINC) complex in force transmission, emphasizing nucleo-cytoskeletal communication in mechanotransduction. The nuclear pore complex (NPC) and its component proteins (<i>i.e.</i> nucleoporins) also play roles in cardiovascular disease (CVD) progression. We herein summarize evidence on the roles of nuclear lamina proteins, LINC complex members, and nucleoporins in endothelial and vascular cell mechanotransduction. Numerous studies attribute NE components in cytoskeletal-related cellular behaviors to insinuate dysregulation of nucleocytoskeletal feedback and nucleocytoplasmic transport as a mechanism of endothelial and vascular dysfunction, and hence implications for aging and vascular pathophysiology.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2453752"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2025-02-12DOI: 10.1080/19491034.2024.2449520
Anjitha Nair, Jayati Khanna, Jashan Kler, Rohith Ragesh, Kundan Sengupta
{"title":"Nuclear envelope and chromatin choreography direct cellular differentiation.","authors":"Anjitha Nair, Jayati Khanna, Jashan Kler, Rohith Ragesh, Kundan Sengupta","doi":"10.1080/19491034.2024.2449520","DOIUrl":"10.1080/19491034.2024.2449520","url":null,"abstract":"<p><p>The nuclear envelope plays an indispensable role in the spatiotemporal organization of chromatin and transcriptional regulation during the intricate process of cell differentiation. This review outlines the distinct regulatory networks between nuclear envelope proteins, transcription factors and epigenetic modifications in controlling the expression of cell lineage-specific genes during differentiation. Nuclear lamina with its associated nuclear envelope proteins organize heterochromatin via Lamina-Associated Domains (LADs), proximal to the nuclear periphery. Since nuclear lamina is mechanosensitive, we critically examine the impact of extracellular forces on differentiation outcomes. The nuclear envelope is spanned by nuclear pore complexes which, in addition to their central role in transport, are associated with chromatin organization. Furthermore, mutations in the nuclear envelope proteins disrupt differentiation, resulting in developmental disorders. Investigating the underlying nuclear envelope controlled regulatory mechanisms of chromatin remodelling during lineage commitment will accelerate our fundamental understanding of developmental biology and regenerative medicine.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2449520"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2025-03-13DOI: 10.1080/19491034.2025.2477848
Thembalami Dube, Dawn M Carone
{"title":"Noncoding RNAs in nuclear organization.","authors":"Thembalami Dube, Dawn M Carone","doi":"10.1080/19491034.2025.2477848","DOIUrl":"10.1080/19491034.2025.2477848","url":null,"abstract":"","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2477848"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2025-02-23DOI: 10.1080/19491034.2025.2468597
Soumya Roy Chowdhury, Arunima Shilpi, Gary Felsenfeld
{"title":"RNA Pol-II transcripts in nucleolar associated domains of cancer cell nucleoli.","authors":"Soumya Roy Chowdhury, Arunima Shilpi, Gary Felsenfeld","doi":"10.1080/19491034.2025.2468597","DOIUrl":"10.1080/19491034.2025.2468597","url":null,"abstract":"<p><p>We performed a comparative study of the non-ribosomal gene content of nucleoli from seven cancer cell lines, using identical methods of purification and analysis. We identified unique chromosomal domains associated with the nucleolus (NADs) and genes within these domains (NAGs). Four cell lines have relatively few NAGs, which appears mostly transcriptionally inactive, consistent with literature. The remaining three lines formed a separate group with nucleoli with unique features and NADS. They constitute larger number of common NAGs, marked by ATAC-seq and having accessible promoters, with histone markers for transcriptional activity and detectable RNA Pol II bound at their promoters. The transcripts of these genes are almost entirely exported from the nucleolus. These results indicate that RNA Pol II dependent transcription in NADs can vary widely in different cell types, presumably dependent on the cell's developmental stage. Nucleolus-associated genes are likely to be distinguished marks reflecting the cell's metabolism.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2468597"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2024-12-25DOI: 10.1080/19491034.2024.2438633
Pierre-Alexandre Vidi, Jing Liu, Keith Bonin, Kerry Bloom
{"title":"Closing the loops: chromatin loop dynamics after DNA damage.","authors":"Pierre-Alexandre Vidi, Jing Liu, Keith Bonin, Kerry Bloom","doi":"10.1080/19491034.2024.2438633","DOIUrl":"10.1080/19491034.2024.2438633","url":null,"abstract":"<p><p>Chromatin is a dynamic polymer in constant motion. These motions are heterogeneous between cells and within individual cell nuclei and are profoundly altered in response to DNA damage. The shifts in chromatin motions following genomic insults depend on the temporal and physical scales considered. They are also distinct in damaged and undamaged regions. In this review, we emphasize the role of chromatin tethering and loop formation in chromatin dynamics, with the view that pulsing loops are key contributors to chromatin motions. Chromatin tethers likely mediate micron-scale chromatin coherence predicted by polymer models and measured experimentally, and we propose that remodeling of the tethers in response to DNA breaks enables uncoupling of damaged and undamaged chromatin regions.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2438633"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2025-05-04DOI: 10.1080/19491034.2025.2498643
Anikó Szabó, Péter Borkúti, Zoltán Kovács, Ildikó Kristó, Péter Vilmos
{"title":"Recent advances in nuclear actin research.","authors":"Anikó Szabó, Péter Borkúti, Zoltán Kovács, Ildikó Kristó, Péter Vilmos","doi":"10.1080/19491034.2025.2498643","DOIUrl":"https://doi.org/10.1080/19491034.2025.2498643","url":null,"abstract":"<p><p>Actin was first observed in the nucleus more than sixty years ago but research on nuclear actin did not receive significant attention for the next forty years. It only started to accelerate around the year 2000, when the first convincing experimental data emerged indicating that actin participates in essential nuclear processes. Today, we know that actin is involved in transcription, replication, DNA repair, chromatin remodeling, and participates in the determination of nuclear shape and size. In this paper we review the results of the last five years of increasingly intensive research on nuclear actin, because on one hand, the field has expanded with several new directions during this time, and on the other hand, the enrichment of our picture of nuclear actin will certainly provide a more solid foundation and new impetus for its future investigation.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2498643"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2025-05-09DOI: 10.1080/19491034.2025.2497765
Giada Forte, Lora Boteva, Nick Gilbert, Peter R Cook, Davide Marenduzzo
{"title":"Bridging-mediated compaction of mitotic chromosomes.","authors":"Giada Forte, Lora Boteva, Nick Gilbert, Peter R Cook, Davide Marenduzzo","doi":"10.1080/19491034.2025.2497765","DOIUrl":"https://doi.org/10.1080/19491034.2025.2497765","url":null,"abstract":"<p><p>Within living cells, chromosome shapes undergo a striking morphological transition, from loose and uncondensed fibers during interphase to compacted and cylindrical structures during mitosis. ATP driven loop extrusion performed by a specialized protein complex, condensin, has recently emerged as a key driver of this transition. However, while this mechanism can successfully recapitulate the compaction of chromatids during the early stages of mitosis, it cannot capture structures observed after prophase. Here we hypothesize that a condensin bridging activity plays an additional important role, and review evidence - obtained largely through molecular dynamics simulations - that, in combination with loop extrusion, it can generate compact metaphase cylinders. Additionally, the resulting model qualitatively explains the unusual elastic properties of mitotic chromosomes observed in micromanipulation experiments and provides insights into the role of condensins in the formation of abnormal chromosome structures associated with common fragile sites.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2497765"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2025-03-13DOI: 10.1080/19491034.2025.2476935
Allysa Sewell, John J Wyrick
{"title":"Interplay of replication timing, DNA repair, and translesion synthesis in UV mutagenesis in yeast.","authors":"Allysa Sewell, John J Wyrick","doi":"10.1080/19491034.2025.2476935","DOIUrl":"10.1080/19491034.2025.2476935","url":null,"abstract":"<p><p>Replication timing during S-phase impacts mutation rates in yeast and human cancers; however, the exact mechanism involved remains unclear. Here, we analyze the impact of replication timing on UV mutagenesis in <i>Saccharomyces cerevisiae</i>. Our analysis indicates that UV mutations are enriched in early-replicating regions of the genome in wild-type cells, but in cells deficient in global genomic-nucleotide excision repair (GG-NER), mutations are enriched in late-replicating regions. Analysis of UV damage maps revealed that cyclobutane pyrimidine dimers are enriched in late-replicating regions, but this enrichment is almost entirely due to repetitive ribosomal DNA. Complex mutations typically associated with TLS activity are also elevated in late-replicating regions in GG-NER deficient cells. We propose that UV mutagenesis is higher in early-replicating regions in repair-competent cells because there is less time to repair the lesion prior to undergoing replication. However, in the absence of GG-NER, increased TLS activity promotes UV mutagenesis in late-replicating regions.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2476935"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}