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https://www.readbyqxmd.com/read/29804820/mis16-switches-function-from-a-histone-h4-chaperone-to-a-cenp-a-cnp1-specific-assembly-factor-through-eic1-interaction
#1
Sojin An, Philipp Koldewey, Jennifer Chik, Lakxmi Subramanian, Uhn-Soo Cho
The Mis18 complex, composed of Mis16, Eic1, and Mis18 in fission yeast, selectively deposits the centromere-specific histone H3 variant, CENP-ACnp1 , at centromeres. How the intact Mis18 holo-complex oligomerizes and how Mis16, a well-known ubiquitous histone H4 chaperone, plays a centromere-specific role in the Mis18 holo-complex, remain unclear. Here, we report the stoichiometry of the intact Mis18 holo-complex as (Mis16)2 :(Eic1)2 :(Mis18)4 using analytical ultracentrifugation. We further determine the crystal structure of Schizosaccharomyces pombe Mis16 in complex with the C-terminal portion of Eic1 (Eic1-CT)...
May 1, 2018: Structure
https://www.readbyqxmd.com/read/29785056/genome-wide-mapping-reveals-that-deoxyuridine-is-enriched-in-the-human-centromeric-dna
#2
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
#3
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/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/29743473/increased-expression-of-holliday-junction-recognizing-protein-hjurp-as-an-independent-prognostic-biomarker-in-advanced-stage-serous-ovarian-carcinoma
#5
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/29626011/centromere-transcription-allows-cenp-a-to-transit-from-chromatin-association-to-stable-incorporation
#6
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...
June 4, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29621654/posttranslational-mechanisms-controlling-centromere-function-and-assembly
#7
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...
June 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29569072/posttranslational-modifications-of-cenp-a-marks-of-distinction
#8
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
#9
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...
April 20, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29522205/chromatin-assembly-factor-1-caf-1-chaperone-regulates-cse4-deposition-into-chromatin-in-budding-yeast
#10
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
https://www.readbyqxmd.com/read/29479426/the-art-of-war-harnessing-the-epigenome-against-cancer
#11
REVIEW
Jonathan Nye, Daniël P Melters, Yamini Dalal
Histone chaperones are indispensable regulators of chromatin structure and function. Recent work has shown that they are frequently mis-regulated in cancer, which can have profound consequences on tumor growth and survival. Here, we focus on chaperones for the essential H3 histone variants H3.3 and CENP-A, specifically HIRA, DAXX/ATRX, DEK, and HJURP. This review summarizes recent studies elucidating their roles in regulating chromatin and discusses how cancer-specific chromatin interactions can be exploited to target cancer cells...
2018: F1000Research
https://www.readbyqxmd.com/read/29466727/in-vivo-analysis-of-centromeric-proteins-reveals-a-stem-cell-specific-asymmetry-and-an-essential-role-in-differentiated-non-proliferating-cells
#12
Ana García Del Arco, Bruce A Edgar, Sylvia Erhardt
Stem cells of the Drosophila midgut (ISCs) are the only mitotically dividing cells of the epithelium and, therefore, presumably the only epithelial cells that require functional kinetochores for microtubule spindle attachment during mitosis. The histone variant CENP-A marks centromeric chromatin as the site of kinetochore formation and spindle attachment during mitotic chromosome segregation. Here, we show that centromeric proteins distribute asymmetrically during ISC division. Whereas newly synthesized CENP-A is enriched in differentiating progeny, CENP-C is undetectable in these cells...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29464982/rcc1-regulates-inner-centromeric-composition-in-a-ran-independent-fashion
#13
Michael Shaofei Zhang, Maiko Furuta, Alexei Arnaoutov, Mary Dasso
RCC1 associates to chromatin dynamically within mitosis and catalyzes Ran-GTP production. Exogenous RCC1 disrupts kinetochore structure in Xenopus egg extracts (XEEs), but the molecular basis of this disruption remains unknown. We have investigated this question, utilizing replicated chromosomes that possess paired sister kinetochores. We find that exogenous RCC1 evicts a specific subset of inner KT proteins including Shugoshin-1 (Sgo1) and the chromosome passenger complex (CPC). We generated RCC1 mutants that separate its enzymatic activity and chromatin binding...
April 5, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29432128/n-terminal-sumoylation-of-centromeric-histone-h3-variant-cse4-regulates-its-proteolysis-to-prevent-mislocalization-to-non-centromeric-chromatin
#14
Kentaro Ohkuni, Reuben Levy-Myers, Jack Warren, Wei-Chun Au, Yoshimitsu Takahashi, Richard E Baker, Munira A Basrai
Stringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4...
March 28, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29416714/mitosis-specific-phosphorylation-of-mis18%C3%AE-by-aurora-b-kinase-enhances-kinetochore-recruitment-of-polo-like-kinase-1
#15
Minkyoung Lee, Ik Soo Kim, Koog Chan Park, Jong-Seo Kim, Sung Hee Baek, Keun Il Kim
Mis18α, a component of Mis18 complex comprising of Mis18α, Mis18β, and M18BP1, is known to localize at the centromere from late telophase to early G1 phase and plays a priming role in CENP-A deposition. Although its role in CENP-A deposition is well established, the other function of Mis18α remains unknown. Here, we elucidate a new function of Mis18α that is critical for the proper progression of cell cycle independent of its role in CENP-A deposition. We find that Aurora B kinase phosphorylates Mis18α during mitosis not affecting neither centromere localization of Mis18 complex nor centromere loading of CENP-A...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29386331/unexpected-conformational-variations-of-the-human-centromeric-chromatin-complex
#16
Jitendra Thakur, Steven Henikoff
We combined classical salt fractionation with chromatin immunoprecipitation to recover human centromeric chromatin under native conditions. We found that >85% of the total centromeric chromatin is insoluble under conditions typically used for native chromatin extraction. To map both soluble and insoluble chromatin in situ, we combined CUT&RUN (cleavage under targets and release using nuclease), a targeted nuclease method, with salt fractionation. Using this approach, we observed unexpected structural and conformational variations of centromere protein A (CENP-A)-containing complexes on different α-satellite dimeric units within highly homogenous arrays...
January 1, 2018: Genes & Development
https://www.readbyqxmd.com/read/29369808/bicaudal-d2-is-a-novel-autoantibody-target-in-systemic-sclerosis-that-shares-a-key-epitope-with-cenp-a-but-has-a-distinct-clinical-phenotype
#17
REVIEW
Marvin J Fritzler, Marie Hudson, May Y Choi, Michael Mahler, Mianbo Wang, Chelsea Bentow, Jay Milo, Murray Baron
We studied the clinical correlations and epitopes of autoantibodies directed to a novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed its relationship to centromere protein A (CENP-A). 451 SSc sera were tested for anti-BICD2 using a paramagnetic bead immunoassay and then univariate and multivariate logistic regression was used to study the association between anti-BICD2 and demographic and clinical parameters as well as other SSc-related autoantibodies. Epitope mapping was performed on solid phase matrices...
March 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29350209/molecular-basis-for-cenp-n-recognition-of-cenp-a-nucleosome-on-the-human-kinetochore
#18
Tian Tian, Xiaorun Li, Yingying Liu, Chengliang Wang, Xing Liu, Guoqiang Bi, Xuan Zhang, Xuebiao Yao, Z Hong Zhou, Jianye Zang
No abstract text is available yet for this article.
March 2018: Cell Research
https://www.readbyqxmd.com/read/29343552/constitutive-centromere-associated-network-contacts-confer-differential-stability-on-cenp-a-nucleosomes-in-vitro-and-in-the-cell
#19
Shengya Cao, Keda Zhou, Zhening Zhang, Karolin Luger, Aaron F Straight
Eukaryotic centromeres are defined by the presence of nucleosomes containing the histone H3 variant, Centromere Protein A (CENP-A). Once incorporated at centromeres, CENP-A nucleosomes are remarkably stable, exhibiting no detectable loss or exchange over many cell cycles. It is currently unclear whether this stability is an intrinsic property of CENP-A containing chromatin or whether it arises from proteins that specifically associate with CENP-A chromatin. Two proteins, CENP-C and CENP-N, are known to bind CENP-A human nucleosomes directly...
January 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29323636/an-optimized-method-for-3d-fluorescence-co-localization-applied-to-human-kinetochore-protein-architecture
#20
Aussie Suzuki, Sarah K Long, Edward D Salmon
Two-color fluorescence co-localization in 3D (three-dimension) has the potential to achieve accurate measurements at the nanometer length scale. Here, we optimized a 3D fluorescence co-localization method that uses mean values for chromatic aberration correction to yield the mean separation with ~10 nm accuracy between green and red fluorescently labeled protein epitopes within single human kinetochores. Accuracy depended critically on achieving small standard deviations in fluorescence centroid determination, chromatic aberration across the measurement field, and coverslip thickness...
January 11, 2018: ELife
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