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Anna A Ye, Stuart Cane, Thomas J Maresca
High-fidelity transmission of the genome through cell division requires that all sister kinetochores bind to dynamic microtubules (MTs) from opposite spindle poles. The application of opposing forces to this bioriented configuration produces tension that stabilizes kinetochore-microtubule (kt-MT) attachments. Defining the magnitude of force that is applied to kinetochores is central to understanding the mechano-molecular underpinnings of chromosome segregation; however, existing kinetochore force measurements span orders of magnitude...
October 20, 2016: Nature Communications
Jing-Hui Zhai, Yi Wu, Xiao-Ying Wang, Yue Cao, Kan Xu, Li Xu, Yi Guo
BACKGROUND It is well known that cerium oxide nanoparticles (CeNPs) have intense antioxidant activity. The antioxidant property of CeNPs are widely used in different areas of research, but little is known about the oxidative damage of Cu2+ associated with Type II diabetes mellitus (T2DM). MATERIAL AND METHODS In our research, the function of CeNPs was tested for its protection of β-cells from the damage of Cu2+ or H2O2. We detected hydroxyl radicals using terephthalic acid assay, hydrogen peroxide using Amplex Ultra Red assay, and cell viability using MTT reduction...
October 18, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Shuai Hou, Na Li, Qian Zhang, Hui Li, Xinyue Wei, Tian Hao, Yue Li, Sikandar Azam, Caigang Liu, Wei Cheng, Bilian Jin, Quentin Liu, Man Li, Haixin Lei
Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is a multi-functional protein that plays critical role in processes including transcription, transcription-coupled DNA repair, pre-mRNA splicing, homologous recombination and mRNA export. Microarray analysis on gene expression in XAB2 knockdown cells reveals that many genes with significant change in expression function in mitotic cell cycle regulation. Fluorescence-activated cell scanner analysis confirmed XAB2 depletion led to cell arrest in G2/M phase, mostly at prophase or prometaphase...
October 13, 2016: Cell Death & Disease
Sylvie Jaillard, Linda Akloul, Marion Beaumont, Houda Hamdi-Roze, Christele Dubourg, Sylvie Odent, Solène Duros, Nathalie Dejucq-Rainsford, Marc-Antoine Belaud-Rotureau, Célia Ravel
BACKGROUND: Ovarian failure (OF) is considered premature if it occurs before the age of 40. This study investigates the genetic aetiology underlying OF in women under the age of 40 years. METHODS: We conducted an experimental prospective study performing all genome microarrays in 60 patients younger than 40 years presenting an OF revealed by a decrease of circulating Anti-Müllerian Hormone (AMH) and leading to an oocyte donation program. RESULTS: We identified nine significant copy number variations (CNVs) including candidate genes potentially implicated in reproductive function...
October 3, 2016: Journal of Ovarian Research
Naoki Wada, Yasuhiro Kazuki, Kanako Kazuki, Toshiaki Inoue, Kiichi Fukui, Mitsuo Oshimura
Replication, segregation, gene expression and inheritance are essential features of all eukaryotic chromosomes. To delineate the extent of conservation of chromosome functions between humans and plants during evolutionary history, we have generated the first human cell line containing an Arabidopsis chromosome. The Arabidopsis chromosome was mitotically stable in hybrid cells following cell division, and initially existed as a translocated chromosome. During culture, the translocated chromosomes then converted to two types of independent plant chromosomes without human DNA sequences, with the reproducibility...
October 4, 2016: ACS Synthetic Biology
Teng Li, Liang Chen, Juanxian Cheng, Jiang Dai, Yijiao Huang, Jian Zhang, Zhaoshan Liu, Ang Li, Na Li, Hongxia Wang, Xiaomin Yin, Kun He, Ming Yu, Tao Zhou, Xuemin Zhang, Qing Xia
Chromosome alignment is required for accurate chromosome segregation. Chromosome misalignment can result in genomic instability and tumorigenesis. Here, we show that NF-κB activating protein (NKAP) is critical for chromosome alignment through anchoring CENP-E to kinetochores. NKAP knockdown causes chromosome misalignment and prometaphase arrest in human cells. NKAP dynamically localizes to kinetochores, and is required for CENP-E kinetochore localization. NKAP is SUMOylated predominantly in mitosis and the SUMOylation is needed for NKAP to bind CENP-E...
October 3, 2016: Nature Communications
Koog Chan Park, Minkyoung Lee, Yoon Jeon, Raok Jeon, Sung Hee Baek, Ho Lee, Keun Il Kim
The Mis18 proteins (Mis18α, Mis18β and M18BP1) are pivotal to the deposition of CENP-A at the centromere during cell cycle progression and are indispensable for embryonic development. Here, we show that Mis18α is critical for the proliferation of keratinocytes and stratification of the epidermis. Mice lacking Mis18α in the epidermis died shortly after birth, showing skin abnormalities like thin and translucent skin as well as defective skin barrier functions. The epidermis of newborn Mis18α-deficient mice lacked distinct stratification and mature hair follicles, with a reduction in the number of proliferating cells and increased cell death in the basal layer...
September 23, 2016: Journal of Investigative Dermatology
Qianhua Dong, Feng-Xiang Yin, Feng Gao, Yuan Shen, Faben Zhang, Yang Li, Haijin He, Marlyn Gonzalez, Jinpu Yang, Shu Zhang, Min Su, Yu-Hang Chen, Fei Li
CENP-A is a centromere-specific histone 3 variant essential for centromere specification. CENP-A partially replaces canonical histone H3 at the centromeres. How the particular CENP-A/H3 ratio at centromeres is precisely maintained is unknown. It also remains unclear how CENP-A is excluded from non-centromeric chromatin. Here, we identify Ccp1, an uncharacterized NAP family protein in fission yeast that antagonizes CENP-A loading at both centromeric and non-centromeric regions. Like the CENP-A loading factor HJURP, Ccp1 interacts with CENP-A and is recruited to centromeres at the end of mitosis in a Mis16-dependent manner...
October 6, 2016: Molecular Cell
Yohei Niikura, Risa Kitagawa, Katsumi Kitagawa
CENP-A (Centromere protein A) is a histone H3 variant that epigenetically determines the centromere position, but the mechanism of its centromere inheritance is obscure. We propose that CENP-A ubiquitylation, which is inherited through dimerization between rounds of cell division, is a candidate for the epigenetic mark of centromere identity.
July 2016: Molecular & Cellular Oncology
Syeda Ridita Sharif, Ariful Islam, Il Soo Moon
N-acetyl-D-glucosamine kinase (GlcNAc kinase or NAGK) primarily catalyzes phosphoryl transfer to GlcNAc during amino sugar metabolism. Recently, it was shown NAGK interacts with dynein light chain roadblock type 1 (DYNLRB1) and upregulates axo-dendritic growth, which is an enzyme activity-independent, non-canonical structural role. The authors examined the distributions of NAGK and NAGK-dynein complexes during the cell cycle in HEK293T cells. NAGK was expressed throughout different stages of cell division and immunocytochemistry (ICC) showed NAGK was localized at nuclear envelope, spindle microtubules (MTs), and kinetochores (KTs)...
September 2016: Molecules and Cells
Lori L Sullivan, Kristin A Maloney, Aaron J Towers, Simon G Gregory, Beth A Sullivan
Centromeres are defined by a specialized chromatin organization that includes nucleosomes that contain the centromeric histone variant centromere protein A (CENP-A) instead of canonical histone H3. Studies in various organisms have shown that centromeric chromatin (i.e., CENP-A chromatin or centrochromatin) exhibits plasticity, in that it can assemble on different types of DNA sequences. However, once established on a chromosome, the centromere is maintained at the same position. In humans, this location is the highly homogeneous repetitive DNA alpha satellite...
August 31, 2016: Chromosome Research
John R Weir, Alex C Faesen, Kerstin Klare, Arsen Petrovic, Federica Basilico, Josef Fischböck, Satyakrishna Pentakota, Jenny Keller, Marion E Pesenti, Dongqing Pan, Doro Vogt, Sabine Wohlgemuth, Franz Herzog, Andrea Musacchio
Chromosomes are carriers of genetic material and their accurate transfer from a mother cell to its two daughters during cell division is of paramount importance for life. Kinetochores are crucial for this process, as they connect chromosomes with microtubules in the mitotic spindle. Kinetochores are multi-subunit complexes that assemble on specialized chromatin domains, the centromeres, that are able to enrich nucleosomes containing the histone H3 variant centromeric protein A (CENP-A). A group of several additional CENPs, collectively known as constitutive centromere associated network (CCAN), establish the inner kinetochore, whereas a ten-subunit assembly known as the KMN network creates a microtubule-binding site in the outer kinetochore...
August 31, 2016: Nature
C Zhang, W Gao, S Wen, Y Wu, R Fu, D Zhao, X Chen, B Wang
To uncover potential key genes, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) associated with laryngeal squamous cell carcinoma (LSCC), microarray data of mRNA, miRNAs and lncRNAs produced from matched sample pairs of LSCC and adjacent normal samples were used to this analysis. Differentially expressed genes (DEGs), miRNAs (DE-miRNAs) and lncRNAs (DE-lncRNAs) were identified, and functions and correlations of them were analyzed. In total, 826 DEGs, 44 DE-miRNAs and 347 DE-lncRNAs were identified. The up-regulated DEGs were mainly related to cell cycle, and the down-regulated DEGs were correlated with regulation of biological quality and extracellular region...
August 27, 2016: Neoplasma
Yuanyuan Kang, Jianbin Wang, Ashley Neff, Stella Kratzer, Hiroshi Kimura, Richard E Davis
The stability of the genome is paramount to organisms. However, diverse eukaryotes carry out programmed DNA elimination in which portions or entire chromsomes are lost in early development or during sex determination. During early development of the parasitic nematode, Ascaris suum, 13% of the genome is eliminated. How different genomic segments are reproducibly retained or discarded is unknown. Here, we show that centromeric histone CENP-A localization plays a key role in this process. We show that Ascaris chromosomes are holocentric during germline mitoses, with CENP-A distributed along their length...
August 30, 2016: Cell Reports
Gülsah Pekgöz Altunkaya, Francesca Malvezzi, Zuzana Demianova, Tomasz Zimniak, Gabriele Litos, Florian Weissmann, Karl Mechtler, Franz Herzog, Stefan Westermann
Partitioning of the genome requires kinetochores, large protein complexes that mediate dynamic attachment of chromosomes to the spindle. Kinetochores contain two supramolecular protein assemblies. The ten-protein KMN network harbors key microtubule-binding sites in the Ndc80 complex and mediates assembly of checkpoint complexes via the KNL-1/Spc105 protein [1, 2]. As KMN does not contact DNA directly, it relies on different centromere-binding proteins for recruitment and cell-cycle-dependent assembly. These proteins are collectively referred to as the CCAN (constitutive centromere-associated network) [2-4]...
September 12, 2016: Current Biology: CB
Yohan Roulland, Khalid Ouararhni, Mladen Naidenov, Lorrie Ramos, Muhammad Shuaib, Sajad Hussain Syed, Imtiaz Nizar Lone, Ramachandran Boopathi, Emeline Fontaine, Gabor Papai, Hiroaki Tachiwana, Thierry Gautier, Dimitrios Skoufias, Kiran Padmanabhan, Jan Bednar, Hitoshi Kurumizaka, Patrick Schultz, Dimitar Angelov, Ali Hamiche, Stefan Dimitrov
CENP-A is a histone variant, which replaces histone H3 at centromeres and confers unique properties to centromeric chromatin. The crystal structure of CENP-A nucleosome suggests flexible nucleosomal DNA ends, but their dynamics in solution remains elusive and their implication in centromere function is unknown. Using electron cryo-microscopy, we determined the dynamic solution properties of the CENP-A nucleosome. Our biochemical, proteomic, and genetic data reveal that higher flexibility of DNA ends impairs histone H1 binding to the CENP-A nucleosome...
August 18, 2016: Molecular Cell
Magdalena Murawska, Andreas G Ladurner
Chaperones mediate vital interactions between histones and DNA during chromatin assembly and reorganization. Two recent studies reveal novel substrates for the essential and conserved histone chaperone FAcilitates Chromatin Transcription (FACT). Prendergast et al. show that FACT helps deposit important histone-fold proteins on centromeres. Raj et al. find that FACT preferentially binds O-GlcNAcylated nucleosomes, suggesting that FACT may contribute to nutrient-regulated cellular programs.
September 2016: Trends in Biochemical Sciences
Yijia Guan, Nan Gao, Jinsong Ren, Xiaogang Qu
Alzheimer's disease (AD) is a complicated multifactorial syndrome. Lessons have been learned through failed clinical trials that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here, we construct core-shell nanoparticles (CeNP@MnMoS4 ) targeting multiple key pathways of the AD pathogenesis, including elimination of toxic metal ions, decrease of oxidative stress, and promotion of neurite outgrowth. The SOD activity and copper removal capacity of CeNP@MnMoS4 -n (n represents the number of layers of MnMoS4 , n=1-5) was investigated in vitro...
October 4, 2016: Chemistry: a European Journal
André Marques, Veit Schubert, Andreas Houben, Andrea Pedrosa-Harand
Centromeres are responsible for the correct segregation of chromosomes during mitosis and meiosis. Holocentric chromosomes, characterized by multiple centromere units along each chromatid, have particular adaptations to ensure regular disjunction during meiosis. Here we show by detecting CENH3, CENP-C, tubulin, and centromeric repeats that holocentromeres may be organized differently in mitosis and meiosis of Rhynchospora pubera Contrasting to the mitotic linear holocentromere organization, meiotic centromeres show several clusters of centromere units (cluster-holocentromeres) during meiosis I...
October 2016: Genetics
Takaharu Hirayama, Masanori Okaniwa, Hiroshi Banno, Hiroyuki Kakei, Akihiro Ohashi, Momoko Ohori, Tadahiro Nambu, Kenichi Iwai, Tomohiro Kawamoto, Akihiro Yokota, Maki Miyamoto, Tomoyasu Ishikawa
Centromere-associated protein-E (CENP-E) is a mitotic kinesin which plays roles in cell division, and is regarded as a promising therapeutic target for the next generation of anti-mitotic agents. We designed novel fused bicyclic CENP-E inhibitors starting from previous reported dihydrobenzofuran derivative (S)-(+)-1. Our design concept was to adjust the electron density distribution on the benzene ring of the dihydrobenzofuran moiety to increase the positive charge for targeting the negatively charged L5 loop of CENP-E, using predictions from electrostatic potential map (EPM) analysis...
September 1, 2016: Bioorganic & Medicinal Chemistry Letters
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