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https://www.readbyqxmd.com/read/28819432/silencing-of-hjurp-induces-dysregulation-of-cell-cycle-and-ros-metabolism-in-bladder-cancer-cells-via-ppar%C3%AE-sirt1-feedback-loop
#1
Rui Cao, Gang Wang, Kaiyu Qian, Liang Chen, Guofeng Qian, Conghua Xie, Han C Dan, Wei Jiang, Min Wu, Chin-Lee Wu, Yu Xiao, Xinghuan Wang
Holliday Junction Recognition Protein (HJURP) is a centromeric histone chaperone involving in de novo histone H3 variant CenH3 (CENP-A) recruitment. Our transcriptome and in vivo study revealed that HJURP is significantly upregulated in bladder cancer (BCa) tissues at both mRNA and protein levels. Knockdown of HJURP inhibited proliferation and viability of BCa cell lines revealed by CCK-8, colony formation and Ki-67-staining assays, and induced apoptosis and reactive oxygen species (ROS) production, as well as triggered cell cycle arrest at G0/G1 phase possibly via loss of CENP-A...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819127/multiple-e3s-promote-the-degradation-of-histone-h3-variant-cse4
#2
Haili Cheng, Xin Bao, Xin Gan, Shiwen Luo, Hai Rao
The histone H3-like protein Cse4/CENP-A acts as a key molecular marker that differentiates the special centromeric chromatin structures from bulk nucleosomes. As altered Cse4/CENP-A activity leads to genome instability, it is pivotal to understand the mechanism underlying Cse4 regulation. Here, we demonstrate that four ubiquitin ligases (i.e., Ubr1, Slx5, Psh1, and Rcy1) work in parallel to promote Cse4 turnover in yeast. Interestingly, Cse4 overexpression leads to cellular toxicity and cell cycle delay in yeast cells lacking PSH1, but not in cells lacking UBR1, suggesting different roles of these two degradation pathways...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28816574/sgt1-hsp90-complex-is-required-for-cenp-a-deposition-at-centromeres
#3
Yohei Niikura, Risa Kitagawa, Hiroo Ogi, Katsumi Kitagawa
The centromere plays an essential role in accurate chromosome segregation, and defects in its function lead to aneuploidy and thus cancer. The centromere-specific histone H3 variant CENP-A is proposed to be the epigenetic mark of the centromere, as active centromeres require CENP-A-containing nucleosomes to direct the recruitment of multiple kinetochore proteins. CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. However, the mechanism that controls the E3 ligase activity of the CUL4A-RBX1-COPS8 complex remains obscure...
August 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28791511/centromere-inheritance-through-the-germline
#4
REVIEW
Arunika Das, Evan M Smoak, Ricardo Linares-Saldana, Michael A Lampson, Ben E Black
The centromere directs chromosome segregation and genetic inheritance but is not itself heritable in a canonical, DNA-based manner. In most species, centromeres are epigenetically defined by the presence of a histone H3 variant centromere protein A (CENP-A), independent of underlying DNA sequence. Therefore, centromere inheritance depends on maintaining the CENP-A nucleosome mark across generations. Experiments in cycling somatic cells have led to a model in which centromere identity is maintained by a cell cycle-coupled CENP-A chromatin assembly pathway...
August 8, 2017: Chromosoma
https://www.readbyqxmd.com/read/28760857/fbw7-loss-promotes-chromosomal-instability-and-tumorigenesis-via-cyclin-e1-cdk2-mediated-phosphorylation-of-cenp-a
#5
Mamoru Takada, Weiguo Zhang, Aussie Suzuki, Taruho Kuroda, Zhouliang Yu, Hiroyuki Inuzuka, Daming Gao, Lixin Wan, Ming Zhuang, Lianxin Hu, Bo Zhai, Christopher Fry, Kerry Bloom, Guohong Li, Gary Karpen, Wenyi Wei, Qing Zhang
The centromere regulates proper chromosome segregation and its dysfunction is implicated in chromosomal instability (CIN). However, relatively little is known about how centromere dysfunction occurs in cancer. Here we define the consequences of phosphorylation by Cyclin E1/CDK2 on a conserved Ser18 residue of centromere-associated protein CENP-A, an essential histone H3 variant that specifies centromere identity. Ser18 hyperphosphorylation in cells occurred upon loss of FBW7, a tumor suppressor whose inactivation leads to chromosomal instability (CIN)...
July 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28756949/expanded-satellite-repeats-amplify-a-discrete-cenp-a-nucleosome-assembly-site-on-chromosomes-that-drive-in-female-meiosis
#6
Aiko Iwata-Otsubo, Jennine M Dawicki-McKenna, Takashi Akera, Samantha J Falk, Lukáš Chmátal, Karren Yang, Beth A Sullivan, Richard M Schultz, Michael A Lampson, Ben E Black
Female meiosis provides an opportunity for selfish genetic elements to violate Mendel's law of segregation by increasing the chance of segregating to the egg [1]. Centromeres and other repetitive sequences can drive in meiosis by cheating the segregation process [2], but the underlying mechanisms are unknown. Here, we show that centromeres with more satellite repeats house more nucleosomes that confer centromere identity, containing the histone H3 variant CENP-A, and bias their segregation to the egg relative to centromeres with fewer repeats...
August 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28749973/replication-stress-affects-the-fidelity-of-nucleosome-mediated-epigenetic-inheritance
#7
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 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28743005/xenopus-laevis-m18bp1-directly-binds-existing-cenp-a-nucleosomes-to-promote-centromeric-chromatin-assembly
#8
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
#9
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
#10
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/28688039/using-human-artificial-chromosomes-to-study-centromere-assembly-and-function
#11
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/28616571/a-time-out-for-cenp-a
#12
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/28598437/centromeres-are-maintained-by-fastening-cenp-a-to-dna-and-directing-an-arginine-anchor-dependent-nucleosome-transition
#13
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
#14
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
#15
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...
July 18, 2017: Oncotarget
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/28489565/motifs-in-the-amino-terminus-of-cenp-a-are-required-for-its-accumulation-within-the-nucleus-and-at-the-centromere
#17
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
#18
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
#19
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/28377371/molecular-basis-for-cdk1-regulated-timing-of-mis18-complex-assembly-and-cenp-a-deposition
#20
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
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