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https://www.readbyqxmd.com/read/28749973/replication-stress-affects-the-fidelity-of-nucleosome-mediated-epigenetic-inheritance
#1
Wenzhu Li, Jia Yi, Pamela Agbu, Zheng Zhou, Richard L Kelley, Scott Kallgren, Songtao Jia, Xiangwei He
The fidelity of epigenetic inheritance or, the precision by which epigenetic information is passed along, is an essential parameter for measuring the effectiveness of the process. How the precision of the process is achieved or modulated, however, remains largely elusive. We have performed quantitative measurement of epigenetic fidelity, using position effect variegation (PEV) in Schizosaccharomyces pombe as readout, to explore whether replication perturbation affects nucleosome-mediated epigenetic inheritance...
July 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28749191/disease-related-autoantibody-profile-in-patients-with-systemic-sclerosis
#2
Christos Liaskos, Emmanouela Marou, Theodora Simopoulou, Maria Barmakoudi, Georgios Efthymiou, Thomas Scheper, Wolfgang Meyer, Dimitrios P Bogdanos, Lazaros I Sakkas
BACKGROUND: Autoantibodies (autoAbs) help in diagnosis and predicting clinical phenotypes in systemic sclerosis (SSc). AIM OF THE STUDY: To determine the clinical utility of 13 SSc-related autoAbs in SSc patients. MATERIAL AND METHODS: A total of 131 consecutive patients with SSc (111 female, mean age 58.1 ± 14 years; 49 with diffused cutaneous SSc [dcSSc] and 82 with limited cutaneous SSc [lcSSc]) were analysed by a multiplex line immunoassay (Euroimmun) for autoantibodies (autoAbs) against 13 SSc-related antigens...
July 27, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28743005/xenopus-laevis-m18bp1-directly-binds-existing-cenp-a-nucleosomes-to-promote-centromeric-chromatin-assembly
#3
Bradley T French, Frederick G Westhorpe, Charles Limouse, Aaron F Straight
Vertebrate centromeres are epigenetically defined by nucleosomes containing the histone H3 variant, CENP-A. CENP-A nucleosome assembly requires the three-protein Mis18 complex (Mis18α, Mis18β, and M18BP1) that recruits the CENP-A chaperone HJURP to centromeres, but how the Mis18 complex recognizes centromeric chromatin is unknown. Using Xenopus egg extract, we show that direct, cell-cycle-regulated binding of M18BP1 to CENP-A nucleosomes recruits the Mis18 complex to interphase centromeres to promote new CENP-A nucleosome assembly...
July 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28743004/association-of-m18bp1-knl2-with-cenp-a-nucleosome-is-essential-for-centromere-formation-in-non-mammalian-vertebrates
#4
Tetsuya Hori, Wei-Hao Shang, Masatoshi Hara, Mariko Ariyoshi, Yasuhiro Arimura, Risa Fujita, Hitoshi Kurumizaka, Tatsuo Fukagawa
Centromeres are specified and maintained by sequence-independent epigenetic mechanisms through the incorporation of CENP-A into centromeres. Given that CENP-A incorporation requires the Mis18 complex to be in the centromere region, it is necessary to precisely understand how the Mis18 complex localizes to the centromere region. Here, we showed that centromere localization of the Mis18 complex depends on CENP-A, but not CENP-C or CENP-T, in chicken DT40 cells. Furthermore, we demonstrated that M18BP1/KNL2, a member of the Mis18 complex, contained the CENP-C-like motif in chicken and other vertebrates, which is essential for centromere localization and M18BP1/KNL2 function in DT40 cells...
July 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28733327/cenp-a-and-topoisomerase-ii-antagonistically-affect-chromosome-length
#5
A-M Ladouceur, Rajesh Ranjan, Lydia Smith, Tanner Fadero, Jennifer Heppert, Bob Goldstein, Amy Shaub Maddox, Paul S Maddox
The size of mitotic chromosomes is coordinated with cell size in a manner dependent on nuclear trafficking. In this study, we conducted an RNA interference screen of the Caenorhabditis elegans nucleome in a strain carrying an exceptionally long chromosome and identified the centromere-specific histone H3 variant CENP-A and the DNA decatenizing enzyme topoisomerase-II (topo-II) as candidate modulators of chromosome size. In the holocentric organism C. elegans, CENP-A is positioned periodically along the entire length of chromosomes, and in mitosis, these genomic regions come together linearly to form the base of kinetochores...
July 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28723232/mechanism-for-g2-phase-specific-nuclear-export-of-the-kinetochore-protein-cenp-f
#6
Kyle M Loftus, Heying Cui, Elias Coutavas, David S King, Amanda Ceravolo, Dylan Pereiras, Sozanne R Solmaz
Centromere protein F (CENP-F) is a component of the kinetochore and a regulator of cell cycle progression. CENP-F recruits the dynein transport machinery and orchestrates several cell cycle-specific transport events, including transport of the nucleus, mitochondria and chromosomes. A key regulatory step for several of these functions is likely the G2 phase-specific export of CENP-F from the nucleus to the cytosol, where the cytoplasmic dynein transport machinery resides; however, the molecular mechanism of this process is elusive...
July 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28701340/cenp-f-couples-cargo-to-growing-and-shortening-microtubule-ends
#7
Gil Kanfer, Martin Peterka, Vladimir K Arzhanik, Alexei L Drobyshev, Fazly I Ataullakhanov, Vladimir A Volkov, Benoît Kornmann
Dynamic microtubule ends exert pulling and pushing forces on intracellular membranes and organelles. However, the mechanical linkage of microtubule tips to their cargoes is poorly understood. CENP-F is a non-motor microtubule-binding protein that participates in microtubule binding at kinetochores and in the mitotic redistribution of the mitochondrial network. CENP-F-driven mitochondrial transport is linked to growing microtubule tips, but the underlying molecular mechanisms are unknown. Here we show that CENP-F tracks growing microtubule ends in living cells...
July 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28688039/using-human-artificial-chromosomes-to-study-centromere-assembly-and-function
#8
REVIEW
Oscar Molina, Natalay Kouprina, Hiroshi Masumoto, Vladimir Larionov, William C Earnshaw
Centromeres are the site of assembly of the kinetochore, which directs chromosome segregation during cell division. Active centromeres are characterized by the presence of nucleosomes containing CENP-A and a specific chromatin environment that resembles that of active genes. Recent work using human artificial chromosomes (HAC) sheds light on the fine balance of different histone post-translational modifications and transcription that exists at centromeres for kinetochore assembly and maintenance. Here, we review the use of HAC technology to understand centromere assembly and function...
July 7, 2017: Chromosoma
https://www.readbyqxmd.com/read/28674240/molecular-genetic-analysis-of-consanguineous-families-with-primary-microcephaly-identified-pathogenic-variants-in-the-aspm-gene
#9
Muzammil Ahmad Khan, Christian Windpassinger, Muhammad Zeeshan Ali, Muhammad Zubair, Hadia Gul, Safdar Abbas, Saadullah Khan, Muhammad Badar, Ramzi M Mohammad, Zafar Nawaz
Autosomal recessive primary microcephaly is a rare genetic disorder that is characterized by reduced head circumference and a varying degree of intellectual disability. Genetic studies on consanguineous families with primary microcephaly have identified 15 (MCPH) causative genes that include MCPH1, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1, CDK6, CENPE, SASS6 MFSD2A ANKLE2 and CIT (Khan et al. 2014; Yamamoto et al. 2014; Alakbarzade et al. 2015;Morris-Rosendahl and Kaindl 2015; Basit et al...
June 2017: Journal of Genetics
https://www.readbyqxmd.com/read/28616571/a-time-out-for-cenp-a
#10
S Hoffmann, D Fachinetti
Proper chromosome segregation relies on a functional centromere-kinetochore interface. We showed that chromatin containing CENtromere Protein A (CENP-A) is essential for centromere assembly, but dispensable for chromosome segregation in the presence of CENP-B-bound DNA sequences. This demonstrates the existence of two contact points between the DNA and the kinetochore to mediate successful chromosome segregation.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28598821/overexpression-of-centromere-protein-k-cenp-k-gene-in-hepatocellular-carcinoma-promote-cell-proliferation-by-activating-akt-tp53-signal-pathway
#11
Haiyan Wang, Weilong Liu, Lei Liu, Chi Wu, Weigang Wu, Juan Zheng, Mingxia Zhang, Xinchun Chen, Boping Zhou, Zhiliang Gao, Jian Huang
Hepatocellular carcinoma (HCC) is one of the high-incidence malignant tumors with very poor prognosis. Identification of potential oncogenes is critical to discovering novel therapeutic targets for many cancers, including HCC. In our previous studies, using microarray technology, we conformed that CENP-K was overexpressed in HCCs. However, whether the overexpression of CENP-K contributes to hepatocarcinogenesis remains unclear. In this study, we found that CENP-K was significantly up-regulated in 60% (63 of 105) of HCC specimens at the mRNA level compared to adjacent non-cancerous liver specimens, as determined by RT-qPCR...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598437/centromeres-are-maintained-by-fastening-cenp-a-to-dna-and-directing-an-arginine-anchor-dependent-nucleosome-transition
#12
Lucie Y Guo, Praveen Kumar Allu, Levani Zandarashvili, Kara L McKinley, Nikolina Sekulic, Jennine M Dawicki-McKenna, Daniele Fachinetti, Glennis A Logsdon, Ryan M Jamiolkowski, Don W Cleveland, Iain M Cheeseman, Ben E Black
Maintaining centromere identity relies upon the persistence of the epigenetic mark provided by the histone H3 variant, centromere protein A (CENP-A), but the molecular mechanisms that underlie its remarkable stability remain unclear. Here, we define the contributions of each of the three candidate CENP-A nucleosome-binding domains (two on CENP-C and one on CENP-N) to CENP-A stability using gene replacement and rapid protein degradation. Surprisingly, the most conserved domain, the CENP-C motif, is dispensable...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28598241/critical-histone-post-translational-modifications-for-centromere-function-and-propagation
#13
Tatsuo Fukagawa
The centromere is a critical genomic region that enables faithful chromosome segregation during mitosis, and must be distinguishable from other genomic regions to facilitate establishment of the kinetochore. The centromere-specific histone H3-variant CENP-A forms a special nucleosome that functions as a marker for centromere specification. In addition to the CENP-A nucleosomes, there are additional H3 nucleosomes that have been identified in centromeres, both of which are predicted to exhibit specific features...
July 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28596481/mislocalization-of-centromeric-histone-h3-variant-cenp-a-contributes-to-chromosomal-instability-cin-in-human-cells
#14
Roshan L Shrestha, Grace S Ahn, Mae I Staples, Kizhakke M Sathyan, Tatiana S Karpova, Daniel R Foltz, Munira A Basrai
Chromosomal instability (CIN) is a hallmark of many cancers and a major contributor to tumorigenesis. Centromere and kinetochore associated proteins such as the evolutionarily conserved centromeric histone H3 variant CENP-A, associate with centromeric DNA for centromere function and chromosomal stability. Stringent regulation of cellular CENP-A levels prevents its mislocalization in yeast and flies to maintain genome stability. CENP-A overexpression and mislocalization are observed in several cancers and reported to be associated with increased invasiveness and poor prognosis...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28587321/clinical-evaluation-of-cenp-b-and-scl-70-autoantibodies-in-silicosis-patients
#15
Suni Lee, Hiroaki Hayashi, Naoko Kumagai-Takei, Hidenori Matsuzaki, Kei Yoshitome, Yasumitsu Nishimura, Kozo Uragami, Masayasu Kusaka, Shoko Yamamoto, Miho Ikeda, Tamayo Hatayama, Wataru Fujimoto, Takemi Otsuki
Silicosis patients (SIL) suffer from respiratory disorders and dysregulation of autoimmunity. Frequent complications such as rheumatoid arthritis, systemic sclerosis (SSc) and vasculitis are known in SIL. Furthermore, we reported previously that some SIL exhibited better respiratory conditions in association with a worse immunological status. In this study, the clinical roles of anti-CENP-B and Scl-70 autoantibodies in SIL were analyzed. The titer index (Log10) of anti-CENP-B autoantibody in SIL was higher than that of healthy volunteers (HV), and that of SSc was higher than those of HV and SIL...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28585134/cenp-a-regulates-chromosome-segregation-during-the-first-meiosis-of-mouse-oocytes
#16
Li Li, Shu-Tao Qi, Qing-Yuan Sun, Shi-Ling Chen
Proper chromosome separation in both mitosis and meiosis depends on the correct connection between kinetochores of chromosomes and spindle microtubules. Kinetochore dysfunction can lead to unequal distribution of chromosomes during cell division and result in aneuploidy, thus kinetochores are critical for faithful segregation of chromosomes. Centromere protein A (CENP-A) is an important component of the inner kinetochore plate. Multiple studies in mitosis have found that deficiencies in CENP-A could result in structural and functional changes of kinetochores, leading to abnormal chromosome segregation, aneuploidy and apoptosis in cells...
June 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28536121/spindle-assembly-checkpoint-satisfaction-occurs-via-end-on-but-not-lateral-attachments-under-tension
#17
Jonathan Kuhn, Sophie Dumont
To ensure accurate chromosome segregation, the spindle assembly checkpoint (SAC) prevents anaphase until all kinetochores attach to the spindle. What signals the SAC monitors remains unclear. We do not know the contributions of different microtubule attachment features or tension from biorientation to SAC satisfaction nor how these possible cues change during attachment. In this study, we quantify concurrent Mad1 intensity and report on SAC silencing, real-time attachment geometry, occupancy, and tension at individual mammalian kinetochores...
June 5, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28498417/cenp-h-regulates-the-cell-growth-of-human-hepatocellular-carcinoma-cells-through-the-mitochondrial-apoptotic-pathway
#18
Guifang Lu, Helei Hou, Xinlan Lu, Xiquan Ke, Xin Wang, Dan Zhang, Yan Zhao, Jun Zhang, Mudan Ren, Shuixiang He
The genomic alterations of hepatocellular carcinoma (HCC) are still unclear. Centromere protein-H (CENP-H) has been shown to be associated with many solid tumors. Our previous study found that CENP-H was upregulated in HCC and was related to patient prognosis. However, the biological functions of CENP-H in HCC and the possible underlying mechanisms have not been well elucidated. In the present study, we demonstrated that CENP-H knockdown inhibited the proliferation of Hep3B cells and decreased colony formation ability of single cells in vitro...
April 26, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28497540/meikin-associated-polo-like-kinase-specifies-bub1-distribution-in-meiosis-i
#19
Seira Miyazaki, Jihye Kim, Yuya Yamagishi, Tadashi Ishiguro, Yuki Okada, Yuji Tanno, Takeshi Sakuno, Yoshinori Watanabe
In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono-orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1...
May 12, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28489565/motifs-in-the-amino-terminus-of-cenp-a-are-required-for-its-accumulation-within-the-nucleus-and-at-the-centromere
#20
Ruiqi Jing, Jiajie Xi, Ye Leng, Wen Chen, Guiying Wang, Wenwen Jia, Jiuhong Kang, Songcheng Zhu
Centromere protein A (CENP-A) is a variant of core histone H3 that marks the centromere's location on the chromosome. The mechanisms that target the protein to the nucleus and the centromere have not been defined. In this study, we found that deletion of the first 53 but not the first 29 residues of CENP-A from the amino-terminus, resulted in its cytoplasmic localization. Two motifs, R42R43R44 and K49R52K53K56, which are reported to be required for DNA contact in the centromere nucleosome, were found to be critical for CENP-A nuclear accumulation...
June 20, 2017: Oncotarget
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