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https://www.readbyqxmd.com/read/28616571/a-time-out-for-cenp-a
#1
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
#2
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
#3
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
#4
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...
June 9, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28473197/identification-and-functional-analysis-of-outer-kinetochore-genes-in-the-holocentric-insect-bombyx-mori
#12
Hiroaki Mon, Jae Man Lee, Masanao Sato, Takahiro Kusakabe
The kinetochore creates chromosomal attachment sites for microtubules. The kinetochore-microtubule interface plays an important role in ensuring accurate transmission of genetic information to daughter cells. Bombyx mori is known to possess holocentric chromosomes, where spindle microtubules attach along the entire length of the chromosome. Recent evidence suggests that CENP-A and CENP-C, which are essential for centromere structure and function in other species, have lost in holocentric insects, implying that B...
May 1, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28396698/internal-modifications-in-the-cenp-a-nucleosome-modulate-centromeric-dynamics
#13
Minh Bui, Mary Pitman, Arthur Nuccio, Serene Roque, Paul Gregory Donlin-Asp, Aleksandra Nita-Lazar, Garegin A Papoian, Yamini Dalal
BACKGROUND: Posttranslational modifications of core histones are correlated with changes in transcriptional status, chromatin fiber folding, and nucleosome dynamics. However, within the centromere-specific histone H3 variant CENP-A, few modifications have been reported, and their functions remain largely unexplored. In this multidisciplinary report, we utilize in silico computational and in vivo approaches to dissect lysine 124 of human CENP-A, which was previously reported to be acetylated in advance of replication...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28395724/-single-nucleotide-polymorphism-of-stat4-rs7574865-is-associated-with-the-susceptibility-of-primary-biliary-cirrhosis-in-han-population-of-partial-regions-of-jiangsu-province
#14
Liming Zheng, Hong Zhou
Objective To investigate the correlation of single nucleotide polymorphism (SNP) of signal transducer and activator of transcription 4 (STAT4) rs7574865 gene with primary biliary cirrhosis (PBC) in Han population of Jiangsu province. Methods The peripheral blood samples were collected from 138 inpatients with PBC and 116 unrelated healthy donors in the Third People's Hospital of Changzhou City in Jiangsu province. The STAT4 rs7574865 SNP was determined by polymerase chain reaction-sequence specific primer (PCR-SSP) assay...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28377371/molecular-basis-for-cdk1-regulated-timing-of-mis18-complex-assembly-and-cenp-a-deposition
#15
Frances Spiller, Bethan Medina-Pritchard, Maria Alba Abad, Martin A Wear, Oscar Molina, William C Earnshaw, A Arockia Jeyaprakash
The centromere, a chromosomal locus that acts as a microtubule attachment site, is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during the cell cycle requires HJURP-mediated CENP-A deposition, a process regulated by the Mis18 complex (Mis18α/Mis18β/Mis18BP1). Spatial and temporal regulation of Mis18 complex assembly is crucial for its centromere association and function. Here, we provide the molecular basis for the assembly and regulation of the Mis18 complex. We show that the N-terminal region of Mis18BP1 spanning amino acid residues 20-130 directly interacts with Mis18α/β to form the Mis18 complex...
June 2017: EMBO Reports
https://www.readbyqxmd.com/read/28356341/essential-role-for-centromeric-factors-following-p53-loss-and-oncogenic-transformation
#16
Dan Filipescu, Monica Naughtin, Katrina Podsypanina, Vincent Lejour, Laurence Wilson, Zachary A Gurard-Levin, Guillermo A Orsi, Iva Simeonova, Eleonore Toufektchan, Laura D Attardi, Franck Toledo, Geneviève Almouzni
In mammals, centromere definition involves the histone variant CENP-A (centromere protein A), deposited by its chaperone, HJURP (Holliday junction recognition protein). Alterations in this process impair chromosome segregation and genome stability, which are also compromised by p53 inactivation in cancer. Here we found that CENP-A and HJURP are transcriptionally up-regulated in p53-null human tumors. Using an established mouse embryonic fibroblast (MEF) model combining p53 inactivation with E1A or HRas-V12 oncogene expression, we reproduced a similar up-regulation of HJURP and CENP-A...
March 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28321116/chromosome-biology-trimethylation-of-cenp-a-supports-mitotic-fidelity
#17
Paulina Strzyz
No abstract text is available yet for this article.
March 21, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28296274/relevance-of-clinical-and-autoantibody-profiles-in-systemic-sclerosis-among-thais
#18
Chingching Foocharoen, Piyakarn Watcharenwong, Sittichai Netwijitpan, Ajanee Mahakkanukrauh, Siraphop Suwannaroj, Ratanavadee Nanagara
OBJECTIVE: Autoantibody profiles in systemic sclerosis (SSc) and their relative clinical association vary between studies. The rate for being anti-topoisomerase-I (ATA) positive and the association with diffuse cutaneous the SSc subset (dcSSc) is higher among Thais than among Caucasians. The objective was to evaluate the relevance of clinical presentation, namely being positive for one or more autoantibodies among Thai SSc patients. METHOD: A retrospective, cohort study was performed among SSc patients over 18 years of age at Srinagarind Hospital, Khon Kaen University, Thailand, during January 2006 to December 2013...
March 10, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28286049/insulin-signaling-regulates-the-foxm1-plk1-cenp-a-pathway-to-promote-adaptive-pancreatic-%C3%AE-%C3%A2-cell-proliferation
#19
Jun Shirakawa, Megan Fernandez, Tomozumi Takatani, Abdelfattah El Ouaamari, Prapaporn Jungtrakoon, Erin R Okawa, Wei Zhang, Peng Yi, Alessandro Doria, Rohit N Kulkarni
Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28266506/%C3%AE-amino-trimethylation-of-cenp-a-by-nrmt-is-required-for-full-recruitment-of-the-centromere
#20
Kizhakke M Sathyan, Daniele Fachinetti, Daniel R Foltz
Centromeres are unique chromosomal domains that control chromosome segregation, and are epigenetically specified by the presence of the CENP-A containing nucleosomes. CENP-A governs centromere function by recruiting the constitutive centromere associated network (CCAN) complex. The features of the CENP-A nucleosome necessary to distinguish centromeric chromatin from general chromatin are not completely understood. Here we show that CENP-A undergoes α-amino trimethylation by the enzyme NRMT in vivo. We show that α-amino trimethylation of the CENP-A tail contributes to cell survival...
March 7, 2017: Nature Communications
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