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Karissa L Milbury, Biplab Paul, Azra Lari, Claire Fowler, Ben Montpetit, Peter C Stirling
The exosome functions to regulate the cellular transcriptome through RNA biogenesis, surveillance, and decay. Through these activities the exosome contributes to many cellular processes, including ribosome biogenesis, mitosis, transcription, and gene silencing. Mutations in Dis3, a catalytic subunit of the RNA exosome with separable endonuclease and exonuclease activities, have recently been linked to the blood cancer multiple myeloma. Here we report that high-throughput genetic interaction screening of a cancer-associated DIS3 allele, dis3E729K , provides evidence for DIS3 functioning to support mitotic fidelity in yeast...
February 6, 2019: Nucleus
Dimitra Paouneskou, Verena Jantsch
Active meiotic chromosome movements are a universally conserved feature. They occur at the early stages of prophase of the first meiotic division and support the chromosome pairing process by (1) efficiently installing the synaptonemal complex between homologous chromosomes, (2) discouraging inadvertent chromosome interactions and (3) bringing homologous chromosomes into proximity. Chromosome movements are driven by forces in the cytoplasm, which are passed on to chromosome ends attached to the nuclear periphery by nuclear-membrane-spanning protein modules...
January 24, 2019: Nucleus
Frida Forsberg, Annaël Brunet, Tharvesh M Liyakat Ali, Philippe Collas
Hepatotoxicity, a major cause of clinical trial failure, can be induced by immunosuppressive drugs such as cyclosporin A (CsA). A mode of CsA action is by regulating nuclear factor binding to target genes, suggesting an impact on genome conformation. To address the link between CsA and chromatin organization, we examined the interactions of A- and B-type nuclear lamins with chromatin, which modulate the radial distribution of the genome. We show that CsA elicits accumulation of pre-lamin A in HepG2 hepatocarcinoma cells, suggesting a rearrangement of lamin-chromatin interactions...
January 20, 2019: Nucleus
Youngjo Kim, Xiaobin Zheng, Yixian Zheng
Genome-wide mapping of lamin-B1-genome interactions has shown that gene-poor and transcriptionally inactive genomic regions are associated with the nuclear lamina. Numerous studies have suggested that lamins, the major structural components of the nuclear lamina, play a role in global chromatin organization and gene expression. How lamins could influence the 3D genome organization and transcription from the nuclear periphery has, however, remained unclear. Our recent studies showed that lamins differentially regulate distinct lamina-associated chromatin domains (LADs) at the nuclear periphery, which can in turn influence global 3D genome organization and gene expression...
December 2019: Nucleus
Romina Burla, Mattia La Torre, Chiara Merigliano, Fiammetta Vernì, Isabella Saggio
Progeroid syndromes induced by mutations in lamin A or in its interactors - named progeroid laminopathies - are model systems for the dissection of the molecular pathways causing physiological and premature aging. A large amount of data, based mainly on the Hutchinson Gilford Progeria syndrome (HGPS), one of the best characterized progeroid laminopathy, has highlighted the role of lamins in multiple DNA activities, including replication, repair, chromatin organization and telomere function. On the other hand, the phenotypes generated by mutations affecting genes directly acting on DNA function, as mutations in the helicases WRN and BLM or in the polymerase polδ, share many of the traits of progeroid laminopathies...
December 31, 2018: Nucleus
Joachim Garbrecht, Harald Hornegger, Sebastien Herbert, Tanja Kaufmann, Josef Gotzmann, Kareem Elsayad, Dea Slade
Fluorescence microscopy in combination with the induction of localized DNA damage using focused light beams has played a major role in the study of protein recruitment kinetics to DNA damage sites in recent years. Currently published methods are dedicated to the study of single fluorophore/single protein kinetics. However, these methods may be limited when studying the relative recruitment dynamics between two or more proteins due to cell-to-cell variability in gene expression and recruitment kinetics, and are not suitable for comparative analysis of fast-recruiting proteins...
September 11, 2018: Nucleus
Tomáš Vacík, Dijana Lađinović, Ivan Raška
Aberrant levels of histone modifications lead to chromatin malfunctioning and consequently to various developmental defects and human diseases. Therefore, the proteins bearing the ability to modify histones have been extensively studied and the molecular mechanisms of their action are now fairly well understood. However, little attention has been paid to naturally occurring alternative isoforms of chromatin modifying proteins and to their biological roles. In this review, we focus on mammalian KDM2A and KDM2B, the only two lysine demethylases whose genes have been described to produce also an alternative isoform lacking the N-terminal demethylase domain...
July 30, 2018: Nucleus
Charlotte Capitanchik, Charles Dixon, Selene K Swanson, Laurence Florens, Alastair R W Kerr, Eric C Schirmer
Nuclear envelopathies/laminopathies yield tissue-specific pathologies, yet arise from mutation of ubiquitously-expressed genes. One possible explanation of this tissue specificity is that tissue-specific partners become disrupted from larger complexes, but a little investigated alternate hypothesis is that the mutated proteins themselves have tissue-specific splice variants. Here, we analyze RNA-Seq datasets to identify muscle-specific splice variants of nuclear envelope genes that could be relevant to the study of laminopathies, particularly muscular dystrophies, that are not currently annotated in sequence databases...
June 18, 2018: Nucleus
Giovanna Lattanzi, Lorenzo Maggi, David Araujo-Vilar
No abstract text is available yet for this article.
2018: Nucleus
Nadya Ilicheva, Olga Podgornaya, Dmitry Bogolyubov, Galina Pochukalina
During the last stages of oogenesis, oocyte chromosomes condense and come close together, forming the so-called karyosphere. Karyosphere formation is accompanied by an essential decrease in transcriptional activity. In the grass frog Rana temporaria, the karyosphere is surrounded by an extrachromosomal capsule that separates the chromosomes from the rest of the nucleoplasm. The karyosphere capsule (KC) of R. temporaria has been investigated in detail at the ultrastructural level, but its protein composition remained largely unknown...
2018: Nucleus
Carmen Mroß, Marija Marko, Martina Munck, Gernot Glöckner, Susanne Motameny, Janine Altmüller, Angelika A Noegel, Ludwig Eichinger, Vivek S Peche, Sascha Neumann
Nesprin-2 is a nuclear envelope component and provides a link between cytoskeletal components of the cytoplasm and the nucleoplasm. Several isoforms are generated from its gene Syne2. Loss of the largest isoform Nesprin-2 Giant in mice is associated with a skin phenotype and altered wound healing, loss of C-terminal isoforms in mice leads to cardiomyopathies and neurological defects. Here we attempted to establish mice with an inducible knockout of all Nesprin-2 isoforms by inserting shRNA encoding sequences targeting the N- and C-terminus into the ROSA26 locus of mice...
2018: Nucleus
Hsin-Yi Chiu, Jack A Bates, Jonas Helma, Hanna Engelke, Hartmann Harz, Thomas Bein, Heinrich Leonhardt
Protein transfection is a versatile tool to study or manipulate cellular processes and also shows great therapeutic potential. However, the repertoire of cost effective techniques for efficient and minimally cytotoxic delivery remains limited. Mesoporous silica nanoparticles (MSNs) are multifunctional nanocarriers for cellular delivery of a wide range of molecules, they are simple and economical to synthesize and have shown great promise for protein delivery. In this work we present a general strategy to optimize the delivery of active protein to the nucleus...
2018: Nucleus
Yasuto Murayama
Cohesin is a ring-shaped, multi-subunit ATPase assembly that is fundamental to the spatiotemporal organization of chromosomes. The ring establishes a variety of chromosomal structures including sister chromatid cohesion and chromatin loops. At the core of the ring is a pair of highly conserved SMC (Structural Maintenance of Chromosomes) proteins, which are closed by the flexible kleisin subunit. In common with other essential SMC complexes including condensin and the SMC5-6 complex, cohesin encircles DNA inside its cavity, with the aid of HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A and TOR) repeat auxiliary proteins...
2018: Nucleus
Varvara V Popova, Alexander V Brechalov, Sofia G Georgieva, Daria V Kopytova
Origin recognition complex (ORC), a heteromeric six-subunit complex, is the central component of the eukaryotic pre-replication complex. Recent data from yeast, frogs, flies and mammals present compelling evidence that ORC and its individual subunits have nonreplicative functions as well. The majority of these functions, such as heterochromatin formation, chromosome condensation, and segregation are dependent on ORC-DNA interactions. Furthermore, ORC is involved in the control of cell division via its participation in centrosome duplication and cytokinesis...
2018: Nucleus
Alessandra Gambineri, Laura Zanotti
Polycystic ovary syndrome (PCOS) is a common disorder with a high phenotypic variability. Frequently, it is associated with a mild to moderate insulin resistance (IR) caused by an interaction between polygenic diathesis and the environment. However, PCOS may be a complication of an underlying syndrome of severe IR such as insulin receptor autoantibodies, mutations in the insulin receptor or in the signalling pathway downstream from the insulin receptor or, most frequently, a defect in function or in the development of the subcutaneous adipose tissue...
2018: Nucleus
Giuseppe Boriani, Elena Biagini, Matteo Ziacchi, Vincenzo Livio Malavasi, Marco Vitolo, Marisa Talarico, Erminio Mauro, Giulia Gorlato, Giovanna Lattanzi
Lamin A/C gene mutations can be associated with cardiac diseases, usually referred to as 'cardiolaminopathies' characterized by arrhythmic disorders and/or left ventricular or biventricular dysfunction up to an overt picture of heart failure. The phenotypic cardiac manifestations of laminopathies are frequently mixed in complex clinical patterns and specifically may include bradyarrhythmias (sinus node disease or atrioventricular blocks), atrial arrhythmias (atrial fibrillation, atrial flutter, atrial standstill), ventricular tachyarrhythmias and heart failure of variable degrees of severity...
2018: Nucleus
Ayantika Sen Gupta, Gaurav Joshi, Sumit Pawar, Kundan Sengupta
Eukaryotic cells have 2 to ​3 discrete nucleoli required for ribosome synthesis. Nucleoli are phase separated nuclear sub-organelles. Here we examined the role of nuclear Lamins and nucleolar factors in modulating the compartmentalization and dynamics of histone 2B (H2B-ECFP) in the nucleolus. Live imaging and Fluorescence Recovery After Photobleaching (FRAP) of labelled H2B, showed that the depletion of Lamin B1, Fibrillarin (FBL) or Nucleostemin (GNL3), enhances H2B-ECFP mobility in the nucleolus. Furthermore, Nucleolin knockdown significantly decreases H2B-ECFP compartmentalization in the nucleolus, while H2B-ECFP residence and mobility in the nucleolus was prolonged upon Nucleolin overexpression...
2018: Nucleus
G Peretto, S Sala, S Benedetti, C Di Resta, L Gigli, M Ferrari, P Della Bella
Cardiac laminopathies, associated with mutations in the LMNA gene, encompass a wide spectrum of clinical manifestations, involving electrical and mechanical alterations of cardiomyocytes. Thus, dilated cardiomyopathy, bradyarrhythmias and atrial or ventricular tachyarrhythmias may occur in a number of combined phenotypes. Nowadays, some attempt has been made to identify clinical predictors for the most life-threatening complications of LMNA-associated heart disease, i.e. sudden cardiac death and end-stage heart failure...
2018: Nucleus
Cristina Cappelletti, Franco Salerno, Eleonora Canioni, Marina Mora, Renato Mantegazza, Pia Bernasconi, Lorenzo Maggi
Laminopathies are a heterogeneous group of diseases, caused by mutations in lamin A/C proteins. The most common laminopathy (LMNA-related myopathies, LMNA-RM) affects skeletal and cardiac muscles; muscle histopathology is variable, ranging from mild unspecific changes to dystrophic features, sometimes with inflammatory evidence. Whether the genetic defect might activate innate immune components, leading to chronic inflammation, myofiber necrosis and fibrosis, is still unknown. By qPCR, a significant up-regulation of Toll-like receptor (TLR) 7 and 9 transcripts was found in LMNA-RM compared to other myopathic and non-myopathic muscles...
2018: Nucleus
(no author information available yet)
No abstract text is available yet for this article.
January 1, 2018: Nucleus
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