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https://www.readbyqxmd.com/read/29785056/genome-wide-mapping-reveals-that-deoxyuridine-is-enriched-in-the-human-centromeric-dna
#1
Xiaoting Shu, Menghao Liu, Zhike Lu, Chenxu Zhu, Haowei Meng, Sihao Huang, Xiaoxue Zhang, Chengqi Yi
Uracil in DNA can be generated by cytosine deamination or dUMP misincorporation; however, its distribution in the human genome is poorly understood. Here we present a selective labeling and pull-down technology for genome-wide uracil profiling and identify thousands of uracil peaks in three different human cell lines. Surprisingly, uracil is highly enriched at the centromere of the human genome. Using mass spectrometry, we demonstrate that human centromeric DNA contains a higher level of uracil. We also directly verify the presence of uracil within two centromeric uracil peaks on chromosomes 6 and 11...
May 21, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29773570/hdna2-nuclease-helicase-promotes-centromeric-dna-replication-and-genome-stability
#2
Zhengke Li, Bochao Liu, Weiwei Jin, Xiwei Wu, Mian Zhou, Vincent Wenzhe Liu, Ajay Goel, Zhiyuan Shen, Li Zheng, Binghui Shen
DNA2 is a nuclease/helicase that is involved in Okazaki fragment maturation, replication fork processing, and end resection of DNA double-strand breaks. Similar such helicase activity for resolving secondary structures and structure-specific nuclease activity are needed during DNA replication to process the chromosome-specific higher order repeat units present in the centromeres of human chromosomes. Here, we show that DNA2 binds preferentially to centromeric DNA The nuclease and helicase activities of DNA2 are both essential for resolution of DNA structural obstacles to facilitate DNA replication fork movement...
May 17, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29765066/loss-of-cenp-f-results-in-dilated-cardiomyopathy-with-severe-disruption-of-cardiac-myocyte-architecture
#3
Annabelle Manalo, Alison K Schroer, Aidan M Fenix, Zoe Shancer, John Coogan, Tanner Brolsma, Dylan T Burnette, W David Merryman, David M Bader
Centromere-binding protein F (CENP-F) is a very large and complex protein with many and varied binding partners including components of the microtubule network. Numerous CENP-F functions impacting diverse cellular behaviors have been identified. Importantly, emerging data have shown that CENP-F loss- or gain-of-function has critical effects on human development and disease. Still, it must be noted that data at the single cardiac myocyte level examining the impact of CENP-F loss-of-function on fundamental cellular behavior is missing...
May 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760389/aurora-a-dependent-cenp-a-phosphorylation-at-inner-centromeres-protects-bioriented-chromosomes-against-cohesion-fatigue
#4
Grégory Eot-Houllier, Laura Magnaghi-Jaulin, Géraldine Fulcrand, François-Xavier Moyroud, Solange Monier, Christian Jaulin
Sustained spindle tension applied to sister centromeres during mitosis eventually leads to uncoordinated loss of sister chromatid cohesion, a phenomenon known as "cohesion fatigue." We report that Aurora A-dependent phosphorylation of serine 7 of the centromere histone variant CENP-A (p-CENP-AS7) protects bioriented chromosomes against cohesion fatigue. Expression of a non-phosphorylatable version of CENP-A (CENP-AS7A) weakens sister chromatid cohesion only when sister centromeres are under tension, providing the first evidence of a regulated mechanism involved in protection against passive cohesion loss...
May 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29748388/the-kinetochore-proteins-cenp-e-and-cenp-f-directly-and-specifically-interact-with-distinct-bub-mitotic-checkpoint-ser-thr-kinases
#5
Giuseppe Ciossani, Katharina Overlack, Arsen Petrovic, Pim J Huis In 't Veld, Carolin Koerner, Sabine Wohlgemuth, Stefano Maffini, Andrea Musacchio
The segregation of chromosomes during cell division relies on the function of the kinetochores, protein complexes that physically connect chromosomes with microtubules of the spindle. The metazoan proteins, centromere protein E (CENP-E) and CENP-F, are components of a fibrous layer of mitotic kinetochores named the corona. Several of their features suggest that CENP-E and CENP-F are paralogs: they are very large (comprising approximately 2700 and 3200 residues, respectively), contain abundant predicted coiled-coil structures, are C-terminally prenylated, and are endowed with microtubule-binding sites at their termini...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29744458/antioxidative-study-of-cerium-oxide-nanoparticle-functionalised-pcl-gelatin-electrospun-fibers-for-wound-healing-application
#6
Hilal Ahmad Rather, Ria Thakore, Ragini Singh, Dhwani Jhala, Sanjay Singh, Rajesh Vasita
Skin wound healing involves a coordinated cellular response to achieve complete reepithelialisation. Elevated levels of reactive oxygen species (ROS) in the wound environment often pose a hindrance in wound healing resulting in impaired wound healing process. Cerium oxide nanoparticles (CeNPs) have the ability to protect the cells from oxidative damage by actively scavenging the ROS. Furthermore, matrices like nanofibers have also been explored for enhancing wound healing. In the current study CeNP functionalised polycaprolactone (PCL)-gelatin nanofiber (PGNPNF) mesh was fabricated by electrospinning and evaluated for its antioxidative potential...
June 2018: Bioactive Materials
https://www.readbyqxmd.com/read/29743473/increased-expression-of-holliday-junction-recognizing-protein-hjurp-as-an-independent-prognostic-biomarker-in-advanced-stage-serous-ovarian-carcinoma
#7
Lin Li, Xiaoli Li, Qin Meng, Abdul Qadir Khan, Xiaomei Chen
BACKGROUND Advanced-stage serous ovarian carcinoma results in the majority of deaths from ovarian carcinoma. The histone chaperone, Holliday junction-recognizing protein (HJURP), binds with centromere protein-A (CENP-A) and its expression has been shown to be a prognostic biomarker in some cancers. The aim of this study was to investigate the role of HJURP expression in advanced-stage serous ovarian carcinoma. MATERIAL AND METHODS Ninety-eight patients with advanced-stage serous ovarian carcinoma, who had tumor tissue samples available, were studied...
May 10, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29725117/cerium-oxide-nanoparticles-with-antioxidant-capabilities-and-gadolinium-integration-for-mri-contrast-enhancement
#8
Peter Eriksson, Alexey A Tal, Andreas Skallberg, Caroline Brommesson, Zhangjun Hu, Robert D Boyd, Weine Olovsson, Neal Fairley, Igor A Abrikosov, Xuanjun Zhang, Kajsa Uvdal
The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue- and cellular level and during tumor treatment to reduce in vivo inflammatory processes...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29701748/mlh1-deficiency-in-normal-mouse-colon-mucosa-associates-with-chromosomally-unstable-colon-cancer
#9
Marjaana Pussila, Petri Törönen, Elisabet Einarsdottir, Shintaro Katayama, Kaarel Krjutškov, Liisa Holm, Juha Kere, Päivi Peltomäki, Markus J Mäkinen, Jere Linden, Minna Nyström
Colorectal cancer (CRC) genome is unstable and different types of instabilities, such as chromosomal instability (CIN) and microsatellite instability (MSI) are thought to reflect distinct cancer initiating mechanisms. Although 85% of sporadic CRC reveal CIN, 15% reveal mismatch repair (MMR) malfunction and MSI, the hallmarks of Lynch syndrome with inherited heterozygous germline mutations in MMR genes. Our study was designed to comprehensively follow genome-wide expression changes and their implications during colon tumorigenesis...
April 26, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29629870/multivalency-of-ndc80-in-the-outer-kinetochore-is-essential-to-track-shortening-microtubules-and-generate-forces
#10
Vladimir A Volkov, Pim J Huis In 't Veld, Marileen Dogterom, Andrea Musacchio
Presence of multiple copies of the microtubule-binding NDC80 complex is an evolutionary conserved feature of kinetochores, points of attachment of chromosomes to spindle microtubules. This may enable multivalent interactions with microtubules, with implications that remain unexplored. Using recombinant human kinetochore components, we show that while single NDC80 complexes do not track depolymerizing microtubules, reconstituted particles containing the NDC80 receptor CENP-T bound to three or more NDC80 complexes do so effectively, as expected for a kinetochore force coupler...
April 9, 2018: ELife
https://www.readbyqxmd.com/read/29626011/centromere-transcription-allows-cenp-a-to-transit-from-chromatin-association-to-stable-incorporation
#11
Georg O M Bobkov, Nick Gilbert, Patrick Heun
Centromeres are essential for chromosome segregation and are specified epigenetically by the presence of the histone H3 variant CENP-A. In flies and humans, replenishment of the centromeric mark is uncoupled from DNA replication and requires the removal of H3 "placeholder" nucleosomes. Although transcription at centromeres has been previously linked to the loading of new CENP-A, the underlying molecular mechanism remains poorly understood. Here, we used Drosophila melanogaster tissue culture cells to show that centromeric presence of actively transcribing RNA polymerase II temporally coincides with de novo deposition of dCENP-A...
April 6, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29621654/posttranslational-mechanisms-controlling-centromere-function-and-assembly
#12
REVIEW
Shashank Srivastava, Ewelina Zasadzińska, Daniel R Foltz
Accurate chromosome segregation is critical to ensure the faithful inheritance of the genome during cell division. Human chromosomes distinguish the location of the centromere from general chromatin by the selective assembly of CENP-A containing nucleosomes at the active centromere. The location of centromeres in most higher eukaryotes is determined epigenetically, independent of DNA sequence. CENP-A containing centromeric chromatin provides the foundation for assembly of the kinetochore that mediates chromosome attachment to the microtubule spindle and controls cell cycle progression in mitosis...
April 2, 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29618387/deregulation-of-the-spindle-assembly-checkpoint-is-associated-with-paclitaxel-resistance-in-ovarian-cancer
#13
Taryne Chong, Amila Sarac, Cindy Q Yao, Linda Liao, Nicola Lyttle, Paul C Boutros, John M S Bartlett, Melanie Spears
BACKGROUND: Ovarian cancer is the leading gynecologic cancer diagnosed in North America and because related symptoms are not disease specific, this often leads to late detection, an advanced disease state, and the need for chemotherapy. Ovarian cancer is frequently sensitive to chemotherapy at diagnosis but rapid development of drug resistance leads to disease progression and ultimately death in the majority of patients. RESULTS: We have generated paclitaxel resistant ovarian cell lines from their corresponding native cell lines to determine driver mechanisms of drug resistance using gene expression arrays...
April 4, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29610759/molecular-signature-of-the-imprintosome-complex-at-the-mating-type-locus-in-fission-yeast
#14
Célia Raimondi, Bernd Jagla, Caroline Proux, Hervé Waxin, Serge Gangloff, Benoit Arcangioli
Genetic and molecular studies have indicated that an epigenetic imprint at mat1 , the sexual locus of fission yeast, initiates mating type switching. The polar DNA replication of mat1 generates an imprint on the Watson strand. The process by which the imprint is formed and maintained through the cell cycle remains unclear. To understand better the mechanism of imprint formation and stability, we characterized the recruitment of early players of mating type switching at the mat1 region. We found that the switch activating protein 1 (Sap1) is preferentially recruited inside the mat1M allele on a sequence ( SS13 ) that enhances the imprint...
January 16, 2018: Microbial Cell
https://www.readbyqxmd.com/read/29607315/antimicrobial-activity-of-cerium-oxide-nanoparticles-on-opportunistic-microorganisms-a-systematic-review
#15
REVIEW
Isabela Albuquerque Passos Farias, Carlos Christiano Lima Dos Santos, Fábio Correia Sampaio
An evaluation of studies of biologically active nanoparticles provides guidance for the synthesis of nanoparticles with the goal of developing new antibiotics/antifungals to combat microbial resistance. This review article focuses on the physicochemical properties of cerium oxide nanoparticles (CeNPs) with antimicrobial activity. Method . This systematic review followed the Guidelines for Transparent Reporting of Systematic Reviews and Meta-Analyses . Results . Studies have confirmed the antimicrobial activity of CeNPs (synthesized by different routes) using nitrate or chloride salt precursors and having sizes less than 54 nm...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29570902/a-transcriptomics-study-of-differentiated-c2c12-myoblasts-identified-novel-functional-responses-to-17%C3%AE-estradiol
#16
JingJing Ding, ZhaoHong Peng, Di Wi, JiaNing Miao, Bo Liu, LiLi Wang
Previous studies of the role of 17β-estradiol (E2) in myoblast differentiation have produced conflicting data. Therefore, this work aimed to determine the role of E2 on myoblast differentiation and specific myofiber formation. Murine C2C12 myoblasts were cultured in proliferation medium or differentiation medium / 10 nM E2. The role of E2 on specific myosin heavy chain (MyHC) or estrogen receptor (ER) expression was examined using real-time quantitative RT-PCR (RT-qPCR). Transcriptome studies of E2 on myoblast differentiation were accomplished by microarray analyses...
March 23, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29569072/posttranslational-modifications-of-cenp-a-marks-of-distinction
#17
REVIEW
Shashank Srivastava, Daniel R Foltz
Centromeres are specialized chromosome domain that serve as the site for kinetochore assembly and microtubule attachment during cell division, to ensure proper segregation of chromosomes. In higher eukaryotes, the identity of active centromeres is marked by the presence of CENP-A (centromeric protein-A), a histone H3 variant. CENP-A forms a centromere-specific nucleosome that acts as a foundation for centromere assembly and function. The posttranslational modification (PTM) of histone proteins is a major mechanism regulating the function of chromatin...
March 22, 2018: Chromosoma
https://www.readbyqxmd.com/read/29565577/generation-of-a-synthetic-human-chromosome-with-two-centromeric-domains-for-advanced-epigenetic-engineering-studies
#18
Elisa Pesenti, Natalay Kouprina, Mikhail Liskovykh, Joan Aurich-Costa, Vladimir Larionov, Hiroshi Masumoto, William C Earnshaw, Oscar Molina
It is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity. However, the pathways leading to the formation and maintenance of centromere chromatin remain poorly characterized due to difficulties of analysis of centromeric repeats in native chromosomes. To address this problem, in our previous studies we generated a human artificial chromosome (HAC) whose centromere contains a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator, the alphoidtetO-HAC...
March 22, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29560129/-hsa-mir-155-5p-drives-aneuploidy-at-early-stages-of-cellular-transformation
#19
Sara Pagotto, Angelo Veronese, Alessandra Soranno, Paola Lanuti, Mirco Di Marco, Marco Vincenzo Russo, Alice Ramassone, Marco Marchisio, Pasquale Simeone, Paolo E Guanciali Franchi, Giandomenico Palka, Renato Mariani Costantini, Carlo M Croce, Rosa Visone
Hsa-miR-155-5p (miR-155) is overexpressed in most solid and hematological malignancies. It promotes loss of genomic integrity in cancer cells by targeting genes involved in microsatellite instability and DNA repair; however, the link between miR-155 and aneuploidy has been scarcely investigated. Here we describe a novel mechanism by which miR-155 causes chromosomal instability. Using osteosarcoma cells (U2OS) and normal human dermal fibroblast (HDF), two well-established models for the study of chromosome congression, we demonstrate that miR-155 targets the spindle checkpoint proteins BUB1, CENP-F, and ZW10, thus compromising chromosome alignment at the metaphase plate...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29522205/chromatin-assembly-factor-1-caf-1-chaperone-regulates-cse4-deposition-into-chromatin-in-budding-yeast
#20
Geetha S Hewawasam, Karthik Dhatchinamoorthy, Mark Mattingly, Chris Seidel, Jennifer L Gerton
Correct localization of the centromeric histone variant CenH3/CENP-A/Cse4 is an important part of faithful chromosome segregation. Mislocalization of CenH3 could affect chromosome segregation, DNA replication and transcription. CENP-A is often overexpressed and mislocalized in cancer genomes, but the underlying mechanisms are not understood. One major regulator of Cse4 deposition is Psh1, an E3 ubiquitin ligase that controls levels of Cse4 to prevent deposition into non-centromeric regions. We present evidence that Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved histone H3/H4 chaperone with subunits shown previously to interact with CenH3 in flies and human cells, regulates Cse4 deposition in budding yeast...
March 7, 2018: Nucleic Acids Research
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