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Nucleus

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https://www.readbyqxmd.com/read/28640691/the-nesprin-cytoskeleton-interface-probed-directly-on-single-nuclei-is-a-mechanically-rich-system
#1
Daniel A Balikov, Sonia K Brady, Ung Hyun Ko, Jennifer H Shin, Jose M de Pereda, Arnoud Sonnenberg, Hak-Joon Sung, Matthew J Lang
The cytoskeleton provides structure and plays an important role in cellular function such as migration, resisting compression forces, and transport. The cytoskeleton also reacts to physical cues such as fluid shear stress or extracellular matrix remodeling by reorganizing filament associations, most commonly focal adhesions and cell-cell cadherin junctions. These mechanical stimuli can result in genome-level changes, and the physical connection of the cytoskeleton to the nucleus provides an optimal conduit for signal transduction by interfacing with nuclear envelope proteins, called nesprins, within the LINC (linker of the nucleus to the cytoskeleton) complex...
June 22, 2017: Nucleus
https://www.readbyqxmd.com/read/28640660/chromosome-territory-relocation-paradigm-during-dna-damage-response-some-insights-from-molecular-biology-to-physics
#2
Sarosh N Fatakia, Mugdha Kulashreshtha, Ishita S Mehta, Basuthkar J Rao
Among the many facets of DNA damage response (DDR), relocation of chromosome territories (CTs) is most intriguing. We have previously reported that cisplatin induced DDR in human dermal fibroblasts led to relocation of CTs 12, 15 from the nuclear periphery to its interior while CTs 19, 17 repositioned from the interior to its periphery. Studies of CT relocation remain nascent as we begin unraveling the role of key players in DDR to demonstrate its mechanistic basis. Consolidating our recent reports, we argue that γH2AX-signaling leads to enhanced recruitment of nuclear myosin 1 (NM1) to chromatin, which via its motor function, results in CT repositioning...
June 22, 2017: Nucleus
https://www.readbyqxmd.com/read/28635493/the-structure-of-lamin-filaments-in-somatic-cells-as-revealed-by-cryo-electron-tomography
#3
Y Turgay, O Medalia
Metazoan nuclei are equipped with nuclear lamina - a thin layer of intermediate filaments (IFs) mostly built of nuclear lamins facing the inner nuclear membrane (INM). The nuclear lamina serves as an interaction hub for INM-proteins, soluble nuclear factors and DNA. It confers structural and mechanical stability to the nucleus, transduces mechanical forces and biochemical signals across the nuclear envelope (NE) and regulates the organization of chromatin. By utilizing cryo-electron tomography (cryo-ET), we recently provided an unprecedented view into the 3D organization of lamin filaments within the lamina meshwork in mammalian somatic cells...
June 21, 2017: Nucleus
https://www.readbyqxmd.com/read/28635365/nucleosomal-organization-and-dna-base-composition-patterns
#4
Alicia García, Sara González, Francisco Antequera
Nucleosomes are the basic units of chromatin. They compact the genome inside the nucleus and regulate the access of proteins to DNA. In the yeast genome, most nucleosomes occupy well-defined positions, which are maintained under many different physiological situations and genetic backgrounds. Although several short sequence elements have been described that favour or reduce the affinity between histones and DNA, the extent to which the DNA sequence affects nucleosome positioning in the genomic context remains unclear...
June 21, 2017: Nucleus
https://www.readbyqxmd.com/read/28628358/h2b-ubiquitination-conserved-molecular-mechanism-diverse-physiologic-functions-of-the-e3-ligase-during-meiosis
#5
Liying Wang, Cunwei Cao, Fang Wang, Jianguo Zhao, Wei Li
RNF20/Bre1 mediated H2B ubiquitination (H2Bub) has various physiologic functions. Recently, we found that H2Bub participates in meiotic recombination by promoting chromatin relaxation during meiosis. We then analyzed the phylogenetic relationships among the E3 ligase for H2Bub, its E2 Rad6 and their partner WW domain-containing adaptor with a coiled-coil (WAC) or Lge1, and found that the molecular mechanism underlying H2Bub is evolutionarily conserved from yeast to mammals. However, RNF20 has diverse physiologic functions in different organisms, which might be caused by the evolutionary divergency of their domain/motif architectures...
June 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28622108/fluctuations-of-pol-i-and-fibrillarin-contents-of-the-nucleoli
#6
M Hornáček, L Kováčik, T Mazel, D Cmarko, E Bártová, I Raška, E Smirnov
Nucleoli are formed on the basis of ribosomal DNA (rDNA) clusters called Nucleolus Organizer Regions (NORs). Each NOR contains multiple genes coding for RNAs of the ribosomal particles. The prominent components of the nucleolar ultrastructure, fibrillar centers (FC) and dense fibrillar components (DFC), together compose FC/DFC units. These units are centers of rDNA transcription by RNA polymerase I (pol I), as well as the early processing events, in which an essential role belongs to fibrillarin. Each FC/DFC unit probably corresponds to a single transcriptionally active gene...
June 16, 2017: Nucleus
https://www.readbyqxmd.com/read/28557611/lamin-a-and-microtubules-collaborate-to-maintain-nuclear-morphology
#7
Zeshan Tariq, Haoyue Zhang, Alexander Chia-Liu, Yang Shen, Yantenew Gete, Zheng-Mei Xiong, Claire Tocheny, Leonard Campanello, Di Wu, Wolfgang Losert, Kan Cao
Lamin A (LA) is a critical structural component of the nuclear lamina. Mutations within the LA gene (LMNA) lead to several human disorders, most striking of which is Hutchinson-Gilford Progeria Syndrome (HGPS), a premature aging disorder. HGPS cells are best characterized by an abnormal nuclear morphology known as nuclear blebbing, which arises due to the accumulation of progerin, a dominant mutant form of LA. The microtubule (MT) network is known to mediate changes in nuclear morphology in the context of specific events such as mitosis, cell polarization, nucleus positioning and cellular migration...
May 30, 2017: Nucleus
https://www.readbyqxmd.com/read/28524723/l1-retrotransposition-is-activated-by-ten-eleven-translocation-protein-1-and-repressed-by-methyl-cpg-binding-proteins
#8
Peng Zhang, Anne K Ludwig, Florian D Hastert, Cathia Rausch, Anne Lehmkuhl, Ines Hellmann, Martha Smets, Heinrich Leonhardt, M Cristina Cardoso
One of the major functions of DNA methylation is the repression of transposable elements, such as the long-interspersed nuclear element 1 (L1). The underlying mechanism(s), however, are unclear. Here, we addressed how retrotransposon activation and mobilization are regulated by methyl-cytosine modifying ten-eleven-translocation (Tet) proteins and how this is modulated by methyl-CpG binding domain (MBD) proteins. We show that Tet1 activates both, endogenous and engineered L1 retrotransposons. Furthermore, we found that Mecp2 and Mbd2 repress Tet1-mediated activation of L1 by preventing 5hmC formation at the L1 promoter...
May 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28463551/comparative-interactomics-provides-evidence-for-functional-specialization-of-the-nuclear-pore-complex
#9
Samson O Obado, Mark C Field, Michael P Rout
The core architecture of the eukaryotic cell was established well over one billion years ago, and is largely retained in all extant lineages. However, eukaryotic cells also possess lineage-specific features, frequently keyed to specific functional requirements. One quintessential core eukaryotic structure is the nuclear pore complex (NPC), responsible for regulating exchange of macromolecules between the nucleus and cytoplasm as well as acting as a nuclear organizational hub. NPC architecture has been best documented in one eukaryotic supergroup, the Opisthokonts (e...
May 2, 2017: Nucleus
https://www.readbyqxmd.com/read/28448740/sequencing-on-the-solid-5500xl-system-in-depth-characterization-of-the-gc-bias
#10
Simone Roeh, Peter Weber, Monika Rex-Haffner, Jan M Deussing, Elisabeth B Binder, Mira Jakovcevski
Different types of sequencing biases have been described and subsequently improved for a variety of sequencing systems, mostly focusing on the widely used Illumina systems. Similar studies are missing for the SOLiD 5500xl system, a sequencer which produced many data sets available to researchers today. Describing and understanding the bias is important to accurately interpret and integrate these published data in various ongoing research projects. We report a particularly strong GC bias for this sequencing system when analyzing a defined gDNA mix of 5 microbes with a wide range of different GC contents (20-72%) when comparing to the expected distribution and Illumina MiSeq data from the same DNA pool...
April 27, 2017: Nucleus
https://www.readbyqxmd.com/read/28430006/evolutionary-changes-in-lamin-expression-in-the-vertebrate-lineage
#11
Reimer Stick, Annette Peter
The nuclear lamina is involved in fundamental nuclear functions and provides mechanical stability to the nucleus. Lamin filaments form a meshwork closely apposed to the inner nuclear membrane and a small fraction of lamins exist in the nuclear interior. Mutations in lamin genes cause severe hereditary diseases, the laminopathies. During vertebrate evolution the lamin protein family has expanded. While most vertebrate genomes contain 4 lamin genes, encoding the lamins A, B1, B2, and LIII, the majority of non-vertebrate genomes harbor only a single lamin gene...
April 21, 2017: Nucleus
https://www.readbyqxmd.com/read/28406743/the-readers-of-unacetylated-p53-represent-a-new-class-of-acidic-domain-proteins
#12
Donglai Wang, Ning Kon, Omid Tavana, Wei Gu
Acetylation of non-histone proteins plays important roles in regulating protein functions but the mechanisms of action are poorly understood. Our recent study uncovered a previously unknown mechanism by which C-terminal domain (CTD) acetylation of p53 serves as a "switch" to determine the interaction between a unique group of acidic domain-containing proteins and p53, as well as revealed that acidic domains may act as a novel class of "readers" for unacetylated p53. However, the properties of acidic domain "readers" are not well elucidated yet...
April 13, 2017: Nucleus
https://www.readbyqxmd.com/read/28406741/bridging-the-dynamics-and-organization-of-chromatin-domains-by-mathematical-modeling
#13
Soya Shinkai, Tadasu Nozaki, Kazuhiro Maeshima, Yuichi Togashi
The genome is 3-dimensionally organized in the cell, and the mammalian genome DNA is partitioned into submegabase-sized chromatin domains. Genome functions are regulated within and across the domains according to their organization, whereas the chromatin itself is highly dynamic. However, the details of such dynamic organization of chromatin domains in living cells remain unclear. To unify chromatin dynamics and organization, we recently demonstrated that structural information of chromatin domains in living human cells can be extracted from analyses of the subdiffusive nucleosome movement using mathematical modeling...
April 13, 2017: Nucleus
https://www.readbyqxmd.com/read/28406740/%C3%AE-satellite-dna-variation-and-function-of-the-human-centromere
#14
Lori L Sullivan, Kimberline Chew, Beth A Sullivan
Genomic variation is a source of functional diversity that is typically studied in genic and non-coding regulatory regions. However, the extent of variation within noncoding portions of the human genome, particularly highly repetitive regions, and the functional consequences are not well understood. Satellite DNA, including α satellite DNA found at human centromeres, comprises up to 10% of the genome, but is difficult to study because its repetitive nature hinders contiguous sequence assemblies. We recently described variation within α satellite DNA that affects centromere function...
April 13, 2017: Nucleus
https://www.readbyqxmd.com/read/28402725/visualization-of-pml-nuclear-import-complexes-reveals-fg-repeat-nucleoporins-at-cargo-retrieval-sites
#15
Anna Lång, Jens Eriksson, Kay Oliver Schink, Emma Lång, Pernille Blicher, Anna Połeć, Andreas Brech, Bjørn Dalhus, Stig Ove Bøe
Selective nuclear import in eukaryotic cells involves sequential interactions between nuclear import receptors and phenylalanine-glycine (FG)-repeat nucleoporins. Traditionally, binding of cargoes to import receptors is perceived as a nuclear pore complex independent event, while interactions between import complexes and nucleoporins are thought to take place at the nuclear pores. However, studies have shown that nucleoporins are mobile and not static within the nuclear pores, suggesting that they may become engaged in nuclear import before nuclear pore entry...
April 12, 2017: Nucleus
https://www.readbyqxmd.com/read/28287898/consequences-of-a-tight-squeeze-nuclear-envelope-rupture-and-repair
#16
Philipp Isermann, Jan Lammerding
Cell migration through tight spaces can induce substantial deformations of the nucleus and cause nuclear envelope (NE) rupture, resulting in uncontrolled exchange of nuclear and cytosolic proteins. These events can cause DNA damage and, in severe cases, nuclear fragmentation, challenging the integrity of the genomic material. Cells overcome NE ruptures during interphase by repairing the NE using components of the endosomal sorting complexes required for transport (ESCRT) machinery. Paralleling the molecular mechanism used during NE reformation in late mitosis, ESCRT-III subunits and the associated AAA-ATPase VPS4B are recruited to NE rupture sites and help restore NE integrity...
March 13, 2017: Nucleus
https://www.readbyqxmd.com/read/28406751/repetitive-dna-loci-and-their-modulation-by-the-non-canonical-nucleic-acid-structures-r-loops-and-g-quadruplexes
#17
REVIEW
Amanda C Hall, Lauren A Ostrowski, Violena Pietrobon, Karim Mekhail
Cells have evolved intricate mechanisms to maintain genome stability despite allowing mutational changes to drive evolutionary adaptation. Repetitive DNA sequences, which represent the bulk of most genomes, are a major threat to genome stability often driving chromosome rearrangements and disease. The major source of repetitive DNA sequences and thus the most vulnerable constituents of the genome are the rDNA (rDNA) repeats, telomeres, and transposable elements. Maintaining the stability of these loci is critical to overall cellular fitness and lifespan...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28406750/sirtuins-and-dna-damage-repair-sirt7-comes-to-play
#18
REVIEW
Berta N Vazquez, Joshua K Thackray, Lourdes Serrano
Aging is characterized by a cumulative loss of genome integrity, which involves chromatin reorganization, transcriptional dysregulation and the accumulation of DNA damage. Sirtuins participate in the protection against these aging processes by promoting genome homeostasis in response to cellular stress. We recently reported that SirT7(-/-) mice suffer from partial embryonic lethality and a progeroid like phenotype. At the cellular level, SIRT7 depletion results in the impaired repair of DNA double-strand breaks (DSBs), one the most dangerous DNA lesions, leading to genome instability...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28406749/nucleosome-repositioning-during-differentiation-of-a-human-myeloid-leukemia-cell-line
#19
Vladimir B Teif, Jan-Philipp Mallm, Tanvi Sharma, David B Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L Olins, Donald E Olins
Cell differentiation is associated with changes in chromatin organization and gene expression. In this study, we examine chromatin structure following differentiation of the human myeloid leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and properties of epichromatin (surface chromatin adjacent to the nuclear envelope)...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28152343/transcriptomes-reflect-the-phenotypes-of-undifferentiated-granulocyte-and-macrophage-forms-of-hl-60-s4-cells
#20
David B Mark Welch, Anna Jauch, Jörg Langowski, Ada L Olins, Donald E Olins
To understand the chromatin changes underlying differential gene expression during induced differentiation of human leukemic HL-60/S4 cells, we conducted RNA-Seq analysis on quadruplicate cultures of undifferentiated, granulocytic- and macrophage-differentiated cell forms. More than half of mapped genes exhibited altered transcript levels in the differentiated cell forms. In general, more genes showed increased mRNA levels in the granulocytic form and in the macrophage form, than showed decreased levels. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in genes that exhibited differential transcript levels after either RA or TPA treatment...
March 4, 2017: Nucleus
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