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https://www.readbyqxmd.com/read/28186195/cenp-a-chromatin-disassembly-in-stressed-and-senescent-murine-cells
#1
Sabrine Hédouin, Giacomo Grillo, Ivana Ivkovic, Guillaume Velasco, Claire Francastel
Centromeres are chromosomal domains essential for genomic stability. We report here the remarkable transcriptional and epigenetic perturbations at murine centromeres in genotoxic stress conditions. A strong and selective transcriptional activation of centromeric repeats is detected within hours. This is followed by disorganization of centromeres with striking delocalization of nucleosomal CENP-A, the key determinant of centromere identity and function, in a mechanism requiring active transcription of centromeric repeats, the DNA Damage Response (DDR) effector ATM and chromatin remodelers/histone chaperones...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167779/integrity-of-the-human-centromere-dna-repeats-is-protected-by-cenp-a-cenp-c-and-cenp-t
#2
Simona Giunta, Hironori Funabiki
Centromeres are highly specialized chromatin domains that enable chromosome segregation and orchestrate faithful cell division. Human centromeres are composed of tandem arrays of α-satellite DNA, which spans up to several megabases. Little is known about the mechanisms that maintain integrity of the long arrays of α-satellite DNA repeats. Here, we monitored centromeric repeat stability in human cells using chromosome-orientation fluorescent in situ hybridization (CO-FISH). This assay detected aberrant centromeric CO-FISH patterns consistent with sister chromatid exchange at the frequency of 5% in primary tissue culture cells, whereas higher levels were seen in several cancer cell lines and during replicative senescence...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28158539/defects-in-methylation-of-arginine-37-on-cenp-a-cse4-are-compensated-by-the-ubiquitin-ligase-complex-ubr2-mub1
#3
Anke Samel, Thi Kim Loan Nguyen, Ann E Ehrenhofer-Murray
No abstract text is available yet for this article.
February 2, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28137567/mass-spectrometry-based-methodology-for-identification-of-native-histone-variant-modifications-from-mammalian-tissues-and-solid-tumors
#4
A G Nuccio, M Bui, Y Dalal, A Nita-Lazar
Histone posttranslational modifications (PTMs) are key epigenetic marks involved in gene silencing or activation. Histone modifications impact chromatin organization and transcriptional processes through the changes in charge density between histones and DNA. They also serve as recognition and binding sites for specific binding proteins. Histone tails and globular cores contain many basic amino acid residues, which are subject to various dynamic modifications, making the modification repertoire extremely diverse...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28125646/kif4-is-essential-for-mouse-oocyte-meiosis
#5
Nicole J Camlin, Eileen A McLaughlin, Janet E Holt
Progression through the meiotic cell cycle must be strictly regulated in oocytes to generate viable embryos and offspring. During mitosis, the kinesin motor protein Kif4 is indispensable for chromosome condensation and separation, midzone formation and cytokinesis. Additionally, the bioactivity of Kif4 is dependent on phosphorylation via Aurora Kinase B and Cdk1, which regulate Kif4 function throughout mitosis. Here, we examine the role of Kif4 in mammalian oocyte meiosis. Kif4 localized in the cytoplasm throughout meiosis I and II, but was also observed to have a dynamic subcellular distribution, associating with both microtubules and kinetochores at different stages of development...
2017: PloS One
https://www.readbyqxmd.com/read/28094382/the-supercoiling-state-of-dna-determines-the-handedness-of-both-h3-and-cenp-a-nucleosomes
#6
R Vlijm, S H Kim, P L De Zwart, Y Dalal, C Dekker
Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted nucleosome assembly, we show that the handedness of the DNA wrapping around the nucleosome core is intrinsically ambidextrous, and depends on the pre-assembly supercoiling state of the DNA, i.e., it is not uniquely determined by the octameric histone core...
January 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/28087831/a-tale-of-two-cenpcs-centromere-localization-of-kinetochore-null-2-and-cenp-c
#7
Jennifer Mach
No abstract text is available yet for this article.
January 13, 2017: Plant Cell
https://www.readbyqxmd.com/read/28073664/extract-of-bulbus-fritillaria-cirrhosa-perturbs-spindle-assembly-checkpoint-induces-mitotic-aberrations-and-genomic-instability-in-human-colon-epithelial-cell-line
#8
Xihan Guo, Juan Ni, Jinglun Xue, Xu Wang
BACKGROUND: Bulbus Fritillaria cirrhosa D. Don (BFC) has been used in China as a folk medicine for the treatment of cough and asthma for more than 2000 years. The antitussive and antiasthmatic effects of BFC have been reported before, nevertheless its toxicity and safety have not been documented. This study investigated the possible effects of BFC on spindle assembly checkpoint (SAC), mitotic fidelity and genomic stability in human NCM460 colon epithelial cells. METHODS: Cells were treated with BFC (0, 20, 40, 80 and 160μg/ml) for 24, 48 and 72h and harvested differently according to the biomarkers observed...
January 7, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28073008/cenp-a-modifications-on-ser68-and-lys124-are-dispensable-for-establishment-maintenance-and-long-term-function-of-human-centromeres
#9
Daniele Fachinetti, Glennis A Logsdon, Amira Abdullah, Evan B Selzer, Don W Cleveland, Ben E Black
CENP-A is a histone H3 variant key to epigenetic specification of mammalian centromeres. Using transient overexpression of CENP-A mutants, two recent reports in Developmental Cell proposed essential centromere functions for post-translational modifications of human CENP-A. Phosphorylation at Ser68 was proposed to have an essential role in CENP-A deposition at centromeres. Blockage of ubiquitination at Lys124 was proposed to abrogate localization of CENP-A to the centromere. Following gene inactivation and replacement in human cells, we demonstrate that CENP-A mutants that cannot be phosphorylated at Ser68 or ubiquitinated at Lys124 assemble efficiently at centromeres during G1, mediate early events in centromere establishment at an ectopic chromosomal locus, and maintain centromere function indefinitely...
January 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28069312/centromeres-drive-a-hard-bargain
#10
REVIEW
Leah F Rosin, Barbara G Mellone
Centromeres are essential chromosomal structures that mediate the accurate distribution of genetic material during meiotic and mitotic cell divisions. In most organisms, centromeres are epigenetically specified and propagated by nucleosomes containing the centromere-specific H3 variant, centromere protein A (CENP-A). Although centromeres perform a critical and conserved function, CENP-A and the underlying centromeric DNA are rapidly evolving. This paradox has been explained by the centromere drive hypothesis, which proposes that CENP-A is undergoing an evolutionary tug-of-war with selfish centromeric DNA...
January 7, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28062749/targeting-of-a-thaliana-knl2-to-centromeres-depends-on-the-conserved-cenpc-k-motif-in-its-c-terminus
#11
Michael Sandmann, Paul Talbert, Dmitri Demidov, Markus Kuhlmann, Twan Rutten, Udo Conrad, Inna Lermontova
KNL2 (KINETOCHORE NULL 2) is involved in recognition of centromeres and in centromeric localization of the centromere-specific histone cenH3. Our study revealed a cenH3 nucleosome-binding CENPC-k motif at the C-terminus of Arabidopsis thaliana KNL2, which is conserved among a wide spectrum of eukaryotes. Centromeric localization of KNL2 is abolished by deletion of the CENPC-k motif and by mutating single conserved amino acids, but can be restored by insertion of the corresponding motif of A. thaliana CENP-C...
January 6, 2017: Plant Cell
https://www.readbyqxmd.com/read/28059702/cdk-regulated-dimerization-of-m18bp1-on-a-mis18-hexamer-is-necessary-for-cenp-a-loading
#12
Dongqing Pan, Kerstin Klare, Arsen Petrovic, Annika Take, Kai Walstein, Priyanka Singh, Arnaud Rondelet, Alexander W Bird, Andrea Musacchio
Centromeres are unique chromosomal loci that promote the assembly of kinetochores, macromolecular complexes that bind spindle microtubules during mitosis. In most organisms, centromeres lack defined genetic features. Rather, they are specified epigenetically by a centromere-specific histone H3 variant, CENP-A. The Mis18 complex, comprising the Mis18α:Mis18β subcomplex and M18BP1, is crucial for CENP-A homeostasis. It recruits the CENP-A-specific chaperone HJURP to centromeres and primes it for CENP-A loading...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28033210/2016-visionary-leader-bob-dent
#13
Brandon Kit Bredimus
The following manuscript is the winning Richard Hader Visionary Leader 2016 entry submitted to Nursing Management in recognition of Dr. Bob Dent, DNP, MBA, RN, NEA-BC, CENP, FACHE, senior vice president, chief operating officer, and CNO for Midland Memorial Hospital in Midland, Tex. Dr. Dent was formally recognized for his achievements before the Keynote Address at Congress2016, November 8, in Las Vegas, Nev. There, he received the award, sponsored by Hackensack Meridian Health.
January 2017: Nursing Management
https://www.readbyqxmd.com/read/28030618/whole-genome-resequencing-of-holstein-bulls-for-indel-discovery-and-identification-of-genes-associated-with-milk-composition-traits-in-dairy-cattle
#14
Jianping Jiang, Yahui Gao, Yali Hou, Wenhui Li, Shengli Zhang, Qin Zhang, Dongxiao Sun
The use of whole-genome resequencing to obtain more information on genetic variation could produce a range of benefits for the dairy cattle industry, especially with regard to increasing milk production and improving milk composition. In this study, we sequenced the genomes of eight Holstein bulls from four half- or full-sib families, with high and low estimated breeding values (EBVs) of milk protein percentage and fat percentage at an average effective depth of 10×, using Illumina sequencing. Over 0.9 million nonredundant short insertions and deletions (indels) [1-49 base pairs (bp)] were obtained...
2016: PloS One
https://www.readbyqxmd.com/read/28017591/a-dual-inhibitory-mechanism-sufficient-to-maintain-cell-cycle-restricted-cenp-a-assembly
#15
Ana Stankovic, Lucie Y Guo, João F Mata, Dani L Bodor, Xing-Jun Cao, Aaron O Bailey, Jeffrey Shabanowitz, Donald F Hunt, Benjamin A Garcia, Ben E Black, Lars E T Jansen
Chromatin featuring the H3 variant CENP-A at the centromere is critical for its mitotic function and epigenetic maintenance. Assembly of centromeric chromatin is restricted to G1 phase through inhibitory action of Cdk1/2 kinases in other phases of the cell cycle. Here, we identify the two key targets sufficient to maintain cell-cycle control of CENP-A assembly. We uncovered a single phosphorylation site in the licensing factor M18BP1 and a cyclin A binding site in the CENP-A chaperone, HJURP, that mediated specific inhibitory phosphorylation...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28012276/molecular-basis-of-outer-kinetochore-assembly-on-cenp-t
#16
Pim J Huis In 't Veld, Sadasivam Jeganathan, Arsen Petrovic, Priyanka Singh, Juliane John, Veronica Krenn, Florian Weissmann, Tanja Bange, Andrea Musacchio
Stable kinetochore-microtubule attachment is essential for cell division. It requires recruitment of outer kinetochore microtubule binders by centromere proteins C and T (CENP-C and CENP-T). To study the molecular requirements of kinetochore formation, we reconstituted the binding of the MIS12 and NDC80 outer kinetochore subcomplexes to CENP-C and CENP-T. Whereas CENP-C recruits a single MIS12:NDC80 complex, we show here that CENP-T binds one MIS12:NDC80 and two NDC80 complexes upon phosphorylation by the mitotic CDK1:Cyclin B complex at three distinct CENP-T sites...
December 24, 2016: ELife
https://www.readbyqxmd.com/read/28007890/multiple-transcriptional-and-post-transcriptional-pathways-collaborate-to-control-sense-and-antisense-rnas-of-tf2-retroelements-in-fission-yeast
#17
Pierre-Luc Mallet, Marc Larochelle, François Bachand
Retrotransposons are mobile genetic elements that colonize eukaryotic genomes by replicating through an RNA intermediate. As retrotransposons can move within the host genome, defense mechanisms have evolved to repress their potential mutagenic activities. In the fission yeast Schizosaccharomyces pombe, the mRNA of Tf2 long terminal repeat retrotransposons is targeted for degradation by the 3'-5' exonucleolytic activity of the exosome-associated protein Rrp6. Here, we show that the nuclear poly(A)-binding protein Pab2 functions with Rrp6 to negatively control Tf2 mRNA accumulation...
February 2017: Genetics
https://www.readbyqxmd.com/read/27940888/constitutive-centromere-associated-network-controls-centromere-drift-in-vertebrate-cells
#18
Tetsuya Hori, Naoko Kagawa, Atsushi Toyoda, Asao Fujiyama, Sadahiko Misu, Norikazu Monma, Fumiaki Makino, Kazuho Ikeo, Tatsuo Fukagawa
Centromeres are specified by sequence-independent epigenetic mechanisms, and the centromere position may drift at each cell cycle, but once this position is specified, it may not be frequently moved. Currently, it is unclear whether the centromere position is stable. To address this question, we systematically analyzed the position of nonrepetitive centromeres in 21 independent clones isolated from a laboratory stock of chicken DT40 cells using chromatin immunoprecipitation combined with massive parallel sequencing analysis with anti-CENP-A antibody...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/27918550/selective-y-centromere-inactivation-triggers-chromosome-shattering-in-micronuclei-and-repair-by-non-homologous-end-joining
#19
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...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27911702/the-unconventional-kinetoplastid-kinetochore-from-discovery-toward-functional-understanding
#20
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
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