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: 2025-04-09DOI: 10.1080/19491034.2025.2486816
Gianna Manning, Andy Li, Nebiyat Eskndir, Marilena Currey, Andrew D Stephens
{"title":"Constitutive heterochromatin controls nuclear mechanics, morphology, and integrity through H3K9me3 mediated chromocenter compaction.","authors":"Gianna Manning, Andy Li, Nebiyat Eskndir, Marilena Currey, Andrew D Stephens","doi":"10.1080/19491034.2025.2486816","DOIUrl":"10.1080/19491034.2025.2486816","url":null,"abstract":"<p><p>Aberrant nuclear morphology is a hallmark of human disease and causes nuclear dysfunction. Perturbed nuclear mechanics via reduced heterochromatin weakens the nucleus resulting in nuclear blebbing and rupture. While the role of heterochromatin is known, the separate roles of constitutive heterochromatin methylation states remains elusive. Using MEF and HT1080 cells, we isolated the individual contribution of constitutive heterochromatin H3K9 methylation states through histone methyltransferase inhibitors. Inhibition of SUV39H1 via Chaetocin downregulates H3K9 trimethylation (me3), while inhibition of G9a via BIX01294 downregulates H3K9 dimethylation (me2). Overall, the loss of H3K9me3 increased nuclear blebbing and rupture in interphase nuclei due to decreased nuclear rigidity from decompaction of chromocenters. Oppositely, loss of H3K9me2 decreased nuclear blebbing and rupture with increased nuclear rigidity and more compact chromocenters. We show that facultative heterochromatin and HP1α are non-essential for chromocenter compaction. Constitutive heterochromatin provides essential nuclear mechanical support to maintain nuclear shape and integrity through chromocenter compaction.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2486816"},"PeriodicalIF":4.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11988277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735915","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":"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":4.5,"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}
Nucleus (Austin, Tex.)Pub Date : 2025-12-01Epub Date: 2025-09-09DOI: 10.1080/19491034.2025.2557113
Ibtissem Benhamza, Laszlo Imre, Zutao Yu, Peter Nanasi, Pialy Sen, Kata Nora Enyedi, Katalin Goda, György Vamosi, Gabor Szabo
{"title":"H2A.Z-nucleosomes are stabilized by the superhelicity-dependent DNA binding of the C-terminal tail of the histone variant.","authors":"Ibtissem Benhamza, Laszlo Imre, Zutao Yu, Peter Nanasi, Pialy Sen, Kata Nora Enyedi, Katalin Goda, György Vamosi, Gabor Szabo","doi":"10.1080/19491034.2025.2557113","DOIUrl":"10.1080/19491034.2025.2557113","url":null,"abstract":"<p><p>Using an in situ nucleosome stability assay based on salt extraction, we identified distinct stability features of H2A.Z-containing nucleosomes linked to alternative interactions of the histone variant's C-terminal tail (Imre et al., Nat. Commun., 2024). In DT40 cells expressing either full-length or C-terminally truncated human H2A.Z1, we show that nucleosome stability is tail-dependent also through the spectacles of intercalator sensitivity, raising the possibility that the tail may bind to DNA in a superhelicity-dependent fashion. Supporting this, fluorescence correlation spectroscopy detected binding of a fluorescent H2A.Z-tail nonapeptide to supercoiled-but not relaxed-plasmid DNA, while a scrambled peptide showed negligible binding. The DNA topology-dependent binding of the unstructured H2A.Z C-terminus, by affecting nucleosome stability, may be of functional significance in various roles of the histone variant, demonstrating the strong interplay between DNA topology and nucleosome stability and exemplifying how it may be exploited by the cell for regulatory purposes.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2557113"},"PeriodicalIF":4.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031309","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: 2025-01-09DOI: 10.1080/19491034.2024.2449500
Jason C Choi
{"title":"Perinuclear organelle trauma at the nexus of cardiomyopathy pathogenesis arising from loss of function <i>LMNA</i> mutation.","authors":"Jason C Choi","doi":"10.1080/19491034.2024.2449500","DOIUrl":"10.1080/19491034.2024.2449500","url":null,"abstract":"<p><p>Over the past 25 years, nuclear envelope (NE) perturbations have been reported in various experimental models with mutations in the <i>LMNA</i> gene. Although the hypothesis that NE perturbations from <i>LMNA</i> mutations are a fundamental feature of striated muscle damage has garnered wide acceptance, the molecular sequalae provoked by the NE damage and how they underlie disease pathogenesis such as cardiomyopathy (<i>LMNA</i> cardiomyopathy) remain poorly understood. We recently shed light on one such consequence, by employing a cardiomyocyte-specific <i>Lmna</i> deletion <i>in vivo</i> in the adult heart. We observed extensive NE perturbations prior to cardiac function deterioration with collateral damage in the perinuclear space. The Golgi is particularly affected, leading to cytoprotective stress responses that are likely disrupted by the progressive deterioration of the Golgi itself. In this review, we discuss the etiology of <i>LMNA</i> cardiomyopathy with perinuclear 'organelle trauma' as the nexus between NE damage and disease pathogenesis.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2449500"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959866","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: 2025-06-13DOI: 10.1080/19491034.2025.2516909
Joan Serrano-Quílez, Susana Rodriguez-Navarro
{"title":"Unraveling gene expression: a beginner's guide from chromatin modifications to mRNA export in <i>Saccharomyces cerevisiae</i>.","authors":"Joan Serrano-Quílez, Susana Rodriguez-Navarro","doi":"10.1080/19491034.2025.2516909","DOIUrl":"10.1080/19491034.2025.2516909","url":null,"abstract":"<p><p>Understanding gene expression requires grasping its multi-step processes, from chromatin remodeling to mRNA export. This manuscript provides an accessible entry point for PhD students and junior postdocs beginning research in this area, using yeast as a model organism. We present a beginner-friendly overview of gene expression, emphasizing the dynamic interplay between chromatin modifications, transcription, mRNA processing, and export. Key topics include chromatin organization, with a focus on H2B ubiquitylation and H3 methylation crosstalk; transcriptional control by RNA polymerase II, including initiation, elongation, and termination; and the export of mRNAs via Mex67-Mtr2, adaptor proteins, and the TREX and TREX-2 complexes at the nuclear pore complex. Relevant examples from yeast genetics, biochemistry, and structural biology illustrate each step. This overview aims to equip new researchers with foundational knowledge and provides references to key studies, current challenges, and open questions in the regulation of gene expression.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"16 1","pages":"2516909"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287502","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}
{"title":"Narrowing down the candidates of beneficial A-to-I RNA editing by comparing the recoding sites with uneditable counterparts.","authors":"Tianyou Zhao, Ling Ma, Shiwen Xu, Wanzhi Cai, Hu Li, Yuange Duan","doi":"10.1080/19491034.2024.2304503","DOIUrl":"10.1080/19491034.2024.2304503","url":null,"abstract":"<p><p>Adar-mediated adenosine-to-inosine (A-to-I) RNA editing mainly occurs in nucleus and diversifies the transcriptome in a flexible manner. It has been a challenging task to identify beneficial editing sites from the sea of total editing events. The functional Ser>Gly auto-recoding site in insect <i>Adar</i> gene has uneditable Ser codons in ancestral nodes, indicating the selective advantage to having an editable status. Here, we extended this case study to more metazoan species, and also looked for all <i>Drosophila</i> recoding events with potential uneditable synonymous codons. Interestingly, in <i>D. melanogaster</i>, the abundant nonsynonymous editing is enriched in the codons that have uneditable counterparts, but the <i>Adar</i> Ser>Gly case suggests that the editable orthologous codons in other species are not necessarily edited. The use of editable <i>versus</i> ancestral uneditable codon is a smart way to infer the selective advantage of RNA editing, and priority might be given to these editing sites for functional studies due to the feasibility to construct an uneditable allele. Our study proposes an idea to narrow down the candidates of beneficial recoding sites. Meanwhile, we stress that the matched transcriptomes are needed to verify the conservation of editing events during evolution.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"15 1","pages":"2304503"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10826634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577285","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 : 2024-12-01Epub Date: 2024-07-01DOI: 10.1080/19491034.2024.2374854
Luv Kishore Srivastava, Allen J Ehrlicher
{"title":"Sensing the squeeze: nuclear mechanotransduction in health and disease.","authors":"Luv Kishore Srivastava, Allen J Ehrlicher","doi":"10.1080/19491034.2024.2374854","DOIUrl":"10.1080/19491034.2024.2374854","url":null,"abstract":"<p><p>The nucleus not only is a repository for DNA but also a center of cellular and nuclear mechanotransduction. From nuclear deformation to the interplay between mechanosensing components and genetic control, the nucleus is poised at the nexus of mechanical forces and cellular function. Understanding the stresses acting on the nucleus, its mechanical properties, and their effects on gene expression is therefore crucial to appreciate its mechanosensitive function. In this review, we examine many elements of nuclear mechanotransduction, and discuss the repercussions on the health of cells and states of illness. By describing the processes that underlie nuclear mechanosensation and analyzing its effects on gene regulation, the review endeavors to open new avenues for studying nuclear mechanics in physiology and diseases.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"15 1","pages":"2374854"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478135","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}