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Centromere protein

Melissa Antoniou-Kourounioti, Michael L Mimmack, Andrew C G Porter, Christine J Farr
Type II topoisomerase enzymes are essential for resolving DNA topology problems arising through various aspects of DNA metabolism. In vertebrates two isoforms are present, one of which (TOP2A) accumulates on chromatin during mitosis. Moreover, TOP2A targets the mitotic centromere during prophase, persisting there until anaphase onset. It is the catalytically-dispensable C-terminal domain of TOP2 that is crucial in determining this isoform-specific behaviour. In this study we show that, in addition to the recently identified chromatin tether domain, several other features of the alpha-C-Terminal Domain (CTD)...
March 12, 2019: International Journal of Molecular Sciences
Gregory T Marczynski, Kenny Petit, Priya Patel
Despite much effort, the bacterial cell cycle has proved difficult to study and understand. Bacteria do not conform to the standard eukaryotic model of sequential cell-cycle phases. Instead, for example, bacteria overlap their phases of chromosome replication and chromosome partitioning. In "eukaryotic terms," bacteria simultaneously perform "S-phase" and "mitosis" whose coordination is absolutely required for rapid growth and survival. In this review, we focus on the signaling "crosstalk," meaning the signaling mechanisms that advantageously commit bacteria to start both chromosome replication and chromosome partitioning...
2019: Frontiers in Microbiology
Marta Mascaraque, Pablo Delgado-Wicke, Alejandra Damian, Silvia Rocío Lucena, Elisa Carrasco, Ángeles Juarranz
Photodynamic therapy (PDT) constitutes a cancer treatment modality based on the administration of a photosensitizer, which accumulates in tumor cells. The subsequent irradiation of the tumoral area triggers the formation of reactive oxygen species responsible for cancer cell death. One of the compounds approved in clinical practice is methyl-aminolevulinate (MAL), a protoporphyrin IX (PpIX) precursor intermediate of heme synthesis. We have identified the mitotic catastrophe (MC) process after MAL-PDT in HeLa human carcinoma cells...
March 11, 2019: International Journal of Molecular Sciences
Jianke Ren, Richard Finney, Kai Ni, Maggie Cam, Kathrin Muegge
Dynamic regulation of chromatin accessibility is a key feature of cellular differentiation during embryogenesis, but the precise factors that control access to chromatin remain largely unknown. Lsh/HELLS is critical for normal development and mutations of Lsh in human cause the ICF (Immune deficiency, Centromeric instability, Facial anomalies) syndrome, a severe immune disorder with multiple organ deficiencies. We report here that Lsh, previously known to regulate DNA methylation level, has a genome wide chromatin remodeling function...
March 12, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Yick Hin Ling, Karen Wing Yee Yuen
In budding yeast, which possesses simple point centromeres, we discovered that all of its centromeres express long noncoding RNAs (cenRNAs), especially in S phase. Induction of cenRNAs coincides with CENP-ACse4 loading time and is dependent on DNA replication. Centromeric transcription is repressed by centromere-binding factor Cbf1 and histone H2A variant H2A.ZHtz1 Deletion of CBF1 and H2A.Z HTZ1 results in an up-regulation of cenRNAs; an increased loss of a minichromosome; elevated aneuploidy; a down-regulation of the protein levels of centromeric proteins CENP-ACse4 , CENP-A chaperone HJURPScm3 , CENP-CMif2 , SurvivinBir1 , and INCENPSli15 ; and a reduced chromatin localization of CENP-ACse4 , CENP-CMif2 , and Aurora BIpl1 When the RNA interference system was introduced to knock down all cenRNAs from the endogenous chromosomes, but not the cenRNA from the circular minichromosome, an increase in minichromosome loss was still observed, suggesting that cenRNA functions in trans to regulate centromere activity...
March 8, 2019: Proceedings of the National Academy of Sciences of the United States of America
Jane Spirkoski, Akshay Shah, Andrew H Reiner, Philippe Collas, Erwan Delbarre
Targeted deposition of histone variant H3.3 into chromatin is paramount for proper regulation of chromatin integrity, particularly in heterochromatic regions including repeats. We have recently shown that the promyelocytic leukemia (PML) protein prevents H3.3 from being deposited in large heterochromatic PML-associated domains (PADs). However, to what extent PML modulates H3.3 loading on chromatin in other areas of the genome remains unexplored. Here, we examined the impact of PML on targeting of H3.3 to genes and repeat regions that reside outside PADs...
March 5, 2019: Biochemical and Biophysical Research Communications
Jun Li, Zhi-Guang Wang, Long-Bin Pang, Rong-Hua Zhang, Ya-Yan Wang
CENPU (centromere protein U), a centromere component essential for mitosis, relates with some cancers progression. However, it is not well illustrated in lung adenocarcinoma (LAC). Here, we aimed to investigate the potential effect of CENPU on LAC progression and prognosis. In this experiment, expression level of CENPU and association between its expression and LAC patients' clinicopathological characteristics and prognosis were analyzed. The proliferation, migration and invasive abilities of LAC cells were determined by CCK-8, colony formation, transwell assays...
March 8, 2019: Bioscience, Biotechnology, and Biochemistry
Ryan D Fine, Nazif Maqani, Mingguang Li, Elizabeth Franck, Jeffrey S Smith
Sir2 is a highly conserved NAD+ -dependent histone deacetylase that functions in heterochromatin formation and promotes replicative lifespan (RLS) in the budding yeast, Saccharomyces cerevisiae Within the yeast rDNA locus, Sir2 is required for efficient cohesin recruitment and maintaining stability of the tandem array. In addition to the previously reported depletion of Sir2 in replicatively aged cells, we discovered that subunits of the Sir2 containing complexes, SIR and RENT, were depleted. Several other rDNA structural protein complexes also exhibited age-related depletion, most notably the cohesin complex...
March 6, 2019: Genetics
Kai-Wei Yu, Ning Zhong, Yu Xiao, Zhen-Yu She
Chromosome congression is essential for faithful chromosome segregation and genomic stability in cell division. Centromere-associated protein E CENP-E, a plus-end-directed kinesin motor, is required for congression of pole-proximal chromosomes in metaphase. CENP-E accumulates at the outer plate of kinetochores and mediates the kinetochore-microtubule capture. CENP-E also transports the chromosomes along spindle microtubules towards the equatorial plate. CENP-E interacts with BubR1, Aurora B and core kinetochore components during kinetochore-microtubule attachment...
February 19, 2019: Biology of the Cell
Jianlin Wang, Haimin Li, Congcong Xia, Xisheng Yang, Bin Dai, Kaishan Tao, Kefeng Dou
Background: Several studies have found that centromere protein K (CENPK) is overexpressed in several tumour types and promotes tumor progression. However, there has been little research on the role of CENPK in the progression of hepatocellular carcinoma (HCC). Materials and methods: The expression of CENPK in HCC tissues was quantified by Western blot and quantitative real-time PCR. Cells were transfected with lentiviral plasmids containing shRNA sequences targeting CENPK and YAP1 to silence the expression of CENPK and YAP1...
2019: OncoTargets and Therapy
Micah P Stumme-Diers, Tommy Stormberg, Zhiqiang Sun, Yuri L Lyubchenko
Chromatin, which is a long chain of nucleosome subunits, is a dynamic system that allows for such critical processes as DNA replication and transcription to take place in eukaryotic cells. The dynamics of nucleosomes provides access to the DNA by replication and transcription machineries, and critically contributes to the molecular mechanisms underlying chromatin functions. Single-molecule studies such as atomic force microscopy (AFM) imaging have contributed significantly to our current understanding of the role of nucleosome structure and dynamics...
January 31, 2019: Journal of Visualized Experiments: JoVE
Stephen M Hinshaw, Stephen C Harrison
Eukaryotic kinetochores connect spindle microtubules to chromosomal centromeres. A group of proteins called the Ctf19 complex (Ctf19c) in yeast and the constitutive centromere associated network (CCAN) in other organisms creates the foundation of a kinetochore. The Ctf19c/CCAN influences the timing of kinetochore assembly, sets its location by associating with a specialized nucleosome containing the histone H3 variant Cse4/CENP-A, and determines the organization of the microtubule attachment apparatus. We present here the structure of a reconstituted 13-subunit Ctf19c determined by cryo-electron microscopy at ~4 Å resolution...
February 14, 2019: ELife
Omar Hamdani, Namrita Dhillon, Tsung-Han S Hsieh, Takahiro Fujita, Josefina Ocampo, Jacob G Kirkland, Josh Lawrimore, Tetsuya J Kobayashi, Brandon Friedman, Derek Fulton, Kenneth Y Wu, Răzvan V Chereji, Masaya Oki, Kerry Bloom, David J Clark, Oliver J Rando, Rohinton T Kamakaka
The genome is packaged and organized in an ordered, non-random manner and specific chromatin segments contact nuclear substructures to mediate this organization. Transfer RNA genes (tDNAs) are binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the role of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacks any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromatin architecture or chromosome tethering and mobility...
February 4, 2019: Molecular and Cellular Biology
Yu-Lan Zhang, He Zhang, Ying-Jie Gao, Lin-Lin Yan, Xin-Yu Yu, Yi-Hong Yang, Wan-Yue Xu, Cui-Xia Pu, Ying Sun
During meiosis, the stepwise release of sister chromatid cohesion is crucial for the equal distribution of genetic material to daughter cells, enabling generation of fertile gametophytes. However, the molecular mechanism that protects centromeric cohesion from release at meiosis I is unclear in Arabidopsis (Arabidopsis thaliana). Here, we report that the protein phosphatase 2A (PP2A) regulatory subunits B'α and B'β participate in the control of sister chromatid separation. The double mutant b'αβ exhibited severe male and female sterility, caused by the lack of a nucleus or presence of an abnormal nucleus in mature microspores and embryo sacs...
January 31, 2019: Plant Physiology
Gabriela Chaufan, Camila Galvano, Mariela Nieves, Marta Dolores Mudry, Maria Del Carmen Rios de Molina, Nancy Beatriz Andrioli
The fungicide agents are a key component in the fruits and vegetables production. The Iprodione residues is one of the pesticide more frequently found in food products. The available data about the cytotoxicity of iprodione and its metabolites are scarce and do not allow to characterize its genotoxic potential and define the risk assessment .The human larynx epidermoid carcinoma cell line (HEp-2) it has been shown to be sensitive to the toxic effects of xenobiotics of different origin and have been often used in citotoxicity and genotoxicity studies...
January 31, 2019: Chemical Research in Toxicology
Laura Tovini, Sarah E McClelland
It has recently emerged that human chromosomes vary between one another in terms of features that impact their behaviour during impaired chromosome segregation, leading to non-random aneuploidy in the daughter cell population. During the process of chromosome congression to the metaphase plate, chromosome movement is guided by kinesin-like proteins, among which centromere-associated protein E (CENP-E) is important to transport chromosomes along the microtubules of the mitotic spindle. It is known that the inhibition of CENP-E notably impairs alignment for a subset of chromosomes, particularly those positioned close to the centrosome at nuclear envelope breakdown ('polar chromosomes'); it is, however, not clear whether chromosome identity could influence this process...
January 26, 2019: Biomolecules
Elise Parey, Anton Crombach
In the nucleus of eukaryotic cells, genomic DNA associates with numerous protein complexes and RNAs, forming the chromatin landscape. Through a genome-wide study of chromatin-associated proteins in Drosophila cells, five major chromatin types were identified as a refinement of the traditional binary division into hetero- and euchromatin. These five types were given colour names in reference to the Greek word chroma. They are defined by distinct but overlapping combinations of proteins and differ in biological and biochemical properties, including transcriptional activity, replication timing, and histone modifications...
January 28, 2019: Genome Biology and Evolution
Hironori Funabiki
For equal chromosome segregation, a pair of kinetochores on each duplicated chromosome must attach to microtubules connecting to opposite poles. The protein kinase Aurora B plays a critical role in destabilizing microtubules attached in a wrong orientation through phosphorylating kinetochore proteins. The mechanism behind this selective destabilization of aberrant attachments remains elusive. While Aurora B is most enriched on the centromere from prophase to metaphase, emerging evidence suggests the importance of Aurora B on microtubules in this process...
January 22, 2019: Current Opinion in Cell Biology
Jia-Cheng Tang, Ke Wu, Xing Zheng, Ming Xu, Yi Dai, Sai-Sai Wei, Xiu-Jun Cai
BACKGROUND: The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH). METHODS: All subjects were randomized to treatment with either vehicle or GSK923295...
February 5, 2019: Chinese Medical Journal
Yohei Niikura, Risa Kitagawa, Katsumi Kitagawa
The centromere plays an essential role in accurate chromosome segregation, and the chromosomal location of the centromere is determined by the presence of a histone H3 variant, centromere protein A (CENP-A), in centromeric nucleosomes. However, the precise mechanisms of deposition, maintenance, and inheritance of CENP-A at centromeres are unclear. We have reported that CENP-A deposition requires ubiquitylation of CENP-A lysine 124 mediated by the E3 ligase activity of Cullin 4A (CUL4A)-RING-box protein 1 (RBX1)-COP9 signalsome complex subunit 8 (COPS8)...
January 22, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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