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https://www.readbyqxmd.com/read/27918550/selective-y-centromere-inactivation-triggers-chromosome-shattering-in-micronuclei-and-repair-by-non-homologous-end-joining
#1
Peter Ly, Levi S Teitz, Dong H Kim, Ofer Shoshani, Helen Skaletsky, Daniele Fachinetti, David C Page, Don W Cleveland
Chromosome missegregation into a micronucleus can cause complex and localized genomic rearrangements known as chromothripsis, but the underlying mechanisms remain unresolved. Here we developed an inducible Y centromere-selective inactivation strategy by exploiting a CENP-A/histone H3 chimaera to directly examine the fate of missegregated chromosomes in otherwise diploid human cells. Using this approach, we identified a temporal cascade of events that are initiated following centromere inactivation involving chromosome missegregation, fragmentation, and re-ligation that span three consecutive cell cycles...
December 5, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27911702/the-unconventional-kinetoplastid-kinetochore-from-discovery-toward-functional-understanding
#2
REVIEW
Bungo Akiyoshi
The kinetochore is the macromolecular protein complex that drives chromosome segregation in eukaryotes. Its most fundamental function is to connect centromeric DNA to dynamic spindle microtubules. Studies in popular model eukaryotes have shown that centromere protein (CENP)-A is critical for DNA-binding, whereas the Ndc80 complex is essential for microtubule-binding. Given their conservation in diverse eukaryotes, it was widely believed that all eukaryotes would utilize these components to make up a core of the kinetochore...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27893298/replication-checkpoint-suppression-and-structure-of-centromeric-dna
#3
Francesco Romeo, Lucia Falbo, Vincenzo Costanzo
Human centromeres contain large amounts of repetitive DNA sequences known as α satellite DNA, which can be difficult to replicate and whose functional role is unclear. Recently, we have characterized protein composition, structural organization and checkpoint response to stalled replication forks of centromeric chromatin reconstituted in Xenopus laevis egg extract. We showed that centromeric DNA has high affinity for SMC2-4 subunits of condensins and for CENP-A, it is enriched for DNA repair factors and suppresses the ATR checkpoint to ensure its efficient replication...
November 28, 2016: Nucleus
https://www.readbyqxmd.com/read/27881301/structure-of-the-mis12-complex-and-molecular-basis-of-its-interaction-with-cenp-c-at-human-kinetochores
#4
Arsen Petrovic, Jenny Keller, Yahui Liu, Katharina Overlack, Juliane John, Yoana N Dimitrova, Simon Jenni, Suzan van Gerwen, Patricia Stege, Sabine Wohlgemuth, Pascaline Rombaut, Franz Herzog, Stephen C Harrison, Ingrid R Vetter, Andrea Musacchio
Kinetochores, multisubunit protein assemblies, connect chromosomes to spindle microtubules to promote chromosome segregation. The 10-subunit KMN assembly (comprising KNL1, MIS12, and NDC80 complexes, designated KNL1C, MIS12C, and NDC80C) binds microtubules and regulates mitotic checkpoint function through NDC80C and KNL1C, respectively. MIS12C, on the other hand, connects the KMN to the chromosome-proximal domain of the kinetochore through a direct interaction with CENP-C. The structural basis for this crucial bridging function of MIS12C is unknown...
November 3, 2016: Cell
https://www.readbyqxmd.com/read/27880912/cenp-a-is-dispensable-for-mitotic-centromere-function-after-initial-centromere-kinetochore-assembly
#5
Sebastian Hoffmann, Marie Dumont, Viviana Barra, Peter Ly, Yael Nechemia-Arbely, Moira A McMahon, Solène Hervé, Don W Cleveland, Daniele Fachinetti
Human centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27858158/structure-of-centromere-chromatin-from-nucleosome-to-chromosomal-architecture
#6
REVIEW
Thomas Schalch, Florian A Steiner
The centromere is essential for the segregation of chromosomes, as it serves as attachment site for microtubules to mediate chromosome segregation during mitosis and meiosis. In most organisms, the centromere is restricted to one chromosomal region that appears as primary constriction on the condensed chromosome and is partitioned into two chromatin domains: The centromere core is characterized by the centromere-specific histone H3 variant CENP-A (also called cenH3) and is required for specifying the centromere and for building the kinetochore complex during mitosis...
November 17, 2016: Chromosoma
https://www.readbyqxmd.com/read/27851699/designing-tomorrow-bringing-our-own-chair%C3%A2-leading-the-conversations
#7
Joan Ellis Beglinger
A highly visible transition occurred earlier this year with the retirement of Pam Thompson, MS, RN, CENP, FAAN, from her role as CEO of the American Organization of Nurse Executives. Ms Thompson was always an advocate of promoting the voice of nursing. This month, the spotlight will shine on a team of nurse leaders who found their voice, got involved, and led the conversation. We will trace their journey as they analyzed their situation, applied the evidence, and used their seat at the table.
December 2016: Journal of Nursing Administration
https://www.readbyqxmd.com/read/27835888/motor-activity-of-centromere-associated-protein-e-contributes-to-its-localization-at-the-center-of-the-midbody-to-regulate-cytokinetic-abscission
#8
Akihiro Ohashi, Momoko Ohori, Kenichi Iwai
Accurate control of cytokinesis is critical for genomic stability to complete high-fidelity transmission of genetic material to the next generation. A number of proteins accumulate in the intercellular bridge (midbody) during cytokinesis, and the dynamics of these proteins are temporally and spatially orchestrated to complete the process. In this study, we demonstrated that localization of centromere-associated protein-E (CENP-E) at the midbody is involved in cytokinetic abscission. The motor activity of CENP-E and the C-terminal midbody localization domain, which includes amino acids 2659-2666 (RYFDNSSL), are involved in the anchoring of CENP-E to the center of the midbody...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27820823/cenp-a-and-h3-nucleosomes-display-a-similar-stability-to-force-mediated-disassembly
#9
Sung Hyun Kim, Rifka Vlijm, Jaco van der Torre, Yamini Dalal, Cees Dekker
Centromere-specific nucleosomes are a central feature of the kinetochore complex during mitosis, in which microtubules exert pulling and pushing forces upon the centromere. CENP-A nucleosomes have been assumed to be structurally unique, thereby providing resilience under tension relative to their H3 canonical counterparts. Here, we directly test this hypothesis by subjecting CENP-A and H3 octameric nucleosomes, assembled on random or on centromeric DNA sequences, to varying amounts of applied force by using single-molecule magnetic tweezers...
2016: PloS One
https://www.readbyqxmd.com/read/27811920/acetylation-of-histone-h4-lysine-5-and-12-is-required-for-cenp-a-deposition-into-centromeres
#10
Wei-Hao Shang, Tetsuya Hori, Frederick G Westhorpe, Kristina M Godek, Atsushi Toyoda, Sadahiko Misu, Norikazu Monma, Kazuho Ikeo, Christopher W Carroll, Yasunari Takami, Asao Fujiyama, Hiroshi Kimura, Aaron F Straight, Tatsuo Fukagawa
Centromeres are specified epigenetically through the deposition of the centromere-specific histone H3 variant CENP-A. However, how additional epigenetic features are involved in centromere specification is unknown. Here, we find that histone H4 Lys5 and Lys12 acetylation (H4K5ac and H4K12ac) primarily occur within the pre-nucleosomal CENP-A-H4-HJURP (CENP-A chaperone) complex, before centromere deposition. We show that H4K5ac and H4K12ac are mediated by the RbAp46/48-Hat1 complex and that RbAp48-deficient DT40 cells fail to recruit HJURP to centromeres and do not incorporate new CENP-A at centromeres...
November 4, 2016: Nature Communications
https://www.readbyqxmd.com/read/27807043/hjurp-interaction-with-the-condensin-ii-complex-during-g1-promotes-cenp-a-deposition
#11
Meghan C Barnhart-Dailey, Prasad Trivedi, P Todd Stukenberg, Daniel R Foltz
Centromeric chromatin is required for kinetochore assembly during mitosis and accurate chromosome segregation. A unique nucleosome containing the histone H3-specific variant CENP-A is the defining feature of centromeric chromatin. In humans, CENP-A nucleosome deposition occurs in early G1 just following mitotic exit at the time when the CENP-A deposition machinery localizes to centromeres. The mechanism by which CENP-A is deposited onto an existing, condensed chromatin template is not understood. Here, we identify the selective association of the CENP-A chaperone HJURP with the condensin II complex and not condensin I...
November 2, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27794026/histone-h4-facilitates-the-proteolysis-of-the-budding-yeast-cenp-acse4-centromeric-histone-variant
#12
Gary M R Deyter, Erica M Hildebrand, Adrienne D Barber, Sue Biggins
The incorporation of histone variants into nucleosomes can alter chromatin-based processes. CENP-A is the histone H3 variant found exclusively at centromeres that serves as an epigenetic mark for centromere identity and is required for kinetochore assembly. CENP-A mislocalization to ectopic sites appears to contribute to genomic instability, transcriptional misregulation, and tumorigenesis, so mechanisms exist to ensure its exclusive localization to centromeres. One conserved process is proteolysis, which is mediated by the Psh1 E3 ubiquitin ligase in Saccharomyces cerevisiae (budding yeast)...
October 28, 2016: Genetics
https://www.readbyqxmd.com/read/27792880/redox-sensitive-cerium-oxide-nanoparticles-protect-human-keratinocytes-from-oxidative-stress-induced-by-glutathione-depletion
#13
Ragini Singh, Ajay Singh Karakoti, William T Self, Sudipta Seal, Sanjay Singh
Cerium oxide nanoparticles (CeNPs) have gathered much attention in the biomedical field due to its unique antioxidant property. It can protect cells and tissues from oxidative stress induced damage due to its auto-regenerative redox cycle. Our study explores the antioxidant and anti-genotoxic behaviour of PEGylated CeNPs towards oxidative insult produced by BSO (Buthionine sulfoximine) in human keratinocytes (HaCaT cells). BSO inhibits the γ-glutamylcysteinesynthetase (γ-GCS) enzyme and thus acts as a glutathione (GSH) depleting agent to modulate the cellular redox potential...
October 28, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27762268/chromosome-biorientation-produces-hundreds-of-piconewtons-at-a-metazoan-kinetochore
#14
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
https://www.readbyqxmd.com/read/27752033/antioxidation-of-cerium-oxide-nanoparticles-to-several-series-of-oxidative-damage-related-to-type-ii-diabetes-mellitus-in-vitro
#15
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
https://www.readbyqxmd.com/read/27735937/xab2-functions-in-mitotic-cell-cycle-progression-via-transcriptional-regulation-of-cenpe
#16
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
https://www.readbyqxmd.com/read/27716277/array-cgh-diagnosis-in-ovarian-failure-identification-of-new-molecular-actors-for-ovarian-physiology
#17
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
https://www.readbyqxmd.com/read/27696824/maintenance-and-function-of-a-plant-chromosome-in-human-cells
#18
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
https://www.readbyqxmd.com/read/27694884/sumoylated-nkap-is-essential-for-chromosome-alignment-by-anchoring-cenp-e-to-kinetochores
#19
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
https://www.readbyqxmd.com/read/27670610/skin-specific-deletion-of-mis18%C3%AE-impedes-proliferation-and-stratification-of-epidermal-keratinocytes
#20
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
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