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https://www.readbyqxmd.com/read/29161777/structure-based-design-and-evaluation-of-synthetic-porphyrin-derivatives-as-g-quadruplex-stabilizing-anticancer-agents
#1
R N Bhadane, D B Meshram, R M Gilhotra
G-quadruplex structures formed in telomeres and proto-oncogene represent a potentially useful target for anticancer drugs. Stabilization of this arrangement may inhibit the further action of different enzymes involved in cancer cell immortalization. In present work structure based drug design and synthesis was carried out on series of meso-substituted porphyrin analogues. The interaction of porphyrin derivatives with G-quadruplex DNA has been explored by virtual screening procedure. Some of the potential binding agents were then synthesized and evaluated in-vitro by MTT and PCR stop assay...
November 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29161615/more-than-a-tad-spatiotemporal-control-of-caulobacter-pili
#2
REVIEW
Johann Mignolet, Gaël Panis, Patrick H Viollier
The Type IV pilus (T4P) is a powerful and sophisticated bacterial nanomachine involved in numerous cellular processes, including adhesion, DNA uptake and motility. Aside from the well-described subtype T4aP of the Gram-negative genera, including Myxococcus, Pseudomonas and Neisseria, the Tad (tight adherence) pilus secretion system re-shuffles homologous parts from other secretion systems along with uncharacterized components into a new type of protein translocation apparatus. A representative of the Tad apparatus, the Caulobacter crescentus pilus assembly (Cpa) machine is built exclusively at the newborn cell pole once per cell cycle...
November 18, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29161564/cell-biology-when-your-own-chromosomes-act-like-foreign-dna
#3
Alexander Spektor, Neil T Umbreit, David Pellman
Two recent papers report the activation of a pro-inflammatory response by cytoplasmic DNA from aberrant nuclear structures called micronuclei. The findings have implications for tumor immunity, immunotherapy biomarker discovery, and possibly the many-sided effects of senescence-associated secretory phenotype.
November 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29161447/dna-polymerase-beta-participates-in-dna-end-joining
#4
Sreerupa Ray, Gregory Breuer, Michelle DeVeaux, Daniel Zelterman, Ranjit Bindra, Joann B Sweasy
DNA double strand breaks (DSBs) are one of the most deleterious lesions and if left unrepaired, they lead to cell death, genomic instability and carcinogenesis. Cells combat DSBs by two pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ), wherein the two DNA ends are re-joined. Recently a back-up NHEJ pathway has been reported and is referred to as alternative NHEJ (aNHEJ), which joins ends but results in deletions and insertions. NHEJ requires processing enzymes including nucleases and polymerases, although the roles of these enzymes are poorly understood...
November 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29161429/crosstalk-between-the-microbiome-and-epigenome-messages-from-bugs
#5
Yufeng Qin, Paul A Wade
Mammals exist in a complicated symbiotic relationship with their gut microbiome, which is postulated to have broad impacts on host health and disease. As omics-based technologies have matured, the potential mechanisms by which the microbiome affects host physiology are being addressed. The gut microbiome, which provides environmental cues, can modify host cell responses to stimuli through alterations in the host epigenome and, ultimately, gene expression. Increasing evidence highlights microbial generation of bioactive compounds that impact the transcriptional machinery in host cells...
November 17, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29161315/transcriptome-analysis-of-plasmid-induced-genes-sheds-light-on-the-role-of-type-i-ifn-as-adjuvant-in-dna-vaccine-against-infectious-salmon-anemia-virus
#6
Mehrdad Sobhkhez, Aleksej Krasnov, Chia Jung Chang, Børre Robertsen
A previous study showed that a plasmid expressing IFNa (pIFNa) strongly enhanced protection and antibody production of a DNA vaccine against infectious salmon anemia virus (ISAV) in Atlantic salmon. The vaccine consisted of a plasmid (pHE) expressing the virus hemagglutinin-esterase as an antigen. To increase the understanding of the adjuvant effect of pIFNa, we here compared transcriptome responses in salmon muscle at the injection site at week 1 and 2 after injection of pIFNa, pHE, plasmid control (pcDNA3...
2017: PloS One
https://www.readbyqxmd.com/read/29161273/enrichment-of-colorectal-cancer-associations-in-functional-regions-insight-for-using-epigenomics-data-in-the-analysis-of-whole-genome-sequence-imputed-gwas-data
#7
Stephanie A Bien, Paul L Auer, Tabitha A Harrison, Conghui Qu, Charles M Connolly, Peyton G Greenside, Sai Chen, Sonja I Berndt, Stéphane Bézieau, Hyun M Kang, Jeroen Huyghe, Hermann Brenner, Graham Casey, Andrew T Chan, John L Hopper, Barbara L Banbury, Jenny Chang-Claude, Stephen J Chanock, Robert W Haile, Michael Hoffmeister, Christian Fuchsberger, Mark A Jenkins, Suzanne M Leal, Mathieu Lemire, Polly A Newcomb, Steven Gallinger, John D Potter, Robert E Schoen, Martha L Slattery, Joshua D Smith, Loic Le Marchand, Emily White, Brent W Zanke, Goncalo R Abeçasis, Christopher S Carlson, Ulrike Peters, Deborah A Nickerson, Anshul Kundaje, Li Hsu
BACKGROUND: The evaluation of less frequent genetic variants and their effect on complex disease pose new challenges for genomic research. To investigate whether epigenetic data can be used to inform aggregate rare-variant association methods (RVAM), we assessed whether variants more significantly associated with colorectal cancer (CRC) were preferentially located in non-coding regulatory regions, and whether enrichment was specific to colorectal tissues. METHODS: Active regulatory elements (ARE) were mapped using data from 127 tissues and cell-types from NIH Roadmap Epigenomics and Encyclopedia of DNA Elements (ENCODE) projects...
2017: PloS One
https://www.readbyqxmd.com/read/29161272/global-transcriptome-profile-reveals-abundance-of-dna-damage-response-and-repair-genes-in-individuals-from-high-level-natural-radiation-areas-of-kerala-coast
#8
Vinay Jain, Birajalaxmi Das
The high level natural radiation areas (HLNRA) of Kerala coast in south west India is unique for its wide variation in the background radiation dose (<1.0mGy to 45mGy/year) and vast population size. Several biological studies conducted in this area did not reveal any adverse effects of chronic low dose and low dose rate radiation on human population. In the present study, global transcriptome analysis was carried out in peripheral blood mono-nuclear cells of 36 individuals belonging to different background dose groups [NLNRA, (Group I, ≤1...
2017: PloS One
https://www.readbyqxmd.com/read/29161263/the-nucleoid-as-a-scaffold-for-the-assembly-of-bacterial-signaling-complexes
#9
Audrey Moine, Leon Espinosa, Eugenie Martineau, Mutum Yaikhomba, P J Jazleena, Deborah Byrne, Emanuele G Biondi, Eugenio Notomista, Matteo Brilli, Virginie Molle, Pananghat Gayathri, Tâm Mignot, Emilia M F Mauriello
The FrzCD chemoreceptor from the gliding bacterium Myxococcus xanthus forms cytoplasmic clusters that occupy a large central region of the cell body also occupied by the nucleoid. In this work, we show that FrzCD directly binds to the nucleoid with its N-terminal positively charged tail and recruits active signaling complexes at this location. The FrzCD binding to the nucleoid occur in a DNA-sequence independent manner and leads to the formation of multiple distributed clusters that explore constrained areas...
November 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29161231/epigenetic-regulation-mechanisms-of-microrna-expression
#10
Sara Morales, Mariano Monzo, Alfons Navarro
MicroRNAs (miRNAs) are single-stranded RNAs of 18-25 nucleotides that regulate gene expression at the post-transcriptional level. They are involved in many physiological and pathological processes, including cell proliferation, apoptosis, development and carcinogenesis. Because of the central role of miRNAs in the regulation of gene expression, their expression needs to be tightly controlled. Here, we summarize the different mechanisms of epigenetic regulation of miRNAs, with a particular focus on DNA methylation and histone modification...
November 21, 2017: Biomolecular Concepts
https://www.readbyqxmd.com/read/29161229/sex-and-dose-specific-effects-of-maternal-bisphenol-a-exposure-on-pancreatic-islets-of-first-and-second-generation-adult-mice-offspring
#11
Amita Bansal, Cetewayo Rashid, Frances Xin, Changhong Li, Erzsebet Polyak, Anna Duemler, Tom van der Meer, Martha Stefaniak, Sana Wajid, Nicolai Doliba, Marisa S Bartolomei, Rebecca A Simmons
BACKGROUND: Exposure to the environmental endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with the increased risk of diabetes and obesity. However, the underlying mechanisms remain unknown. We recently demonstrated that perinatal BPA exposure is associated with higher body fat, impaired glucose tolerance, and reduced insulin secretion in first- (F1) and second-generation (F2) C57BL/6J male mice offspring. OBJECTIVE: We sought to determine the multigenerational effects of maternal bisphenol A exposure on mouse pancreatic islets...
September 27, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29161169/investigation-of-apoptosis-in-cultured-cells-infected-with-equine-herpesvirus-1
#12
M R Scrochi, C N Zanuzzi, N Fuentealba, F Nishida, M E Bravi, M E Pacheco, G H Sguazza, E J Gimeno, E L Portiansky, C I Muglia, C M Galosi, C G Barbeito
Many viruses alter different stages of apoptosis of infected cells as a strategy for successful infection. Few studies have addressed mechanisms of equine herpesvirus 1 (EHV-1) strain-induced cell death. We investigated the effect of an abortigenic strain (AR8 strain) on heterologous Madin-Darby bovine kidney cells and homologous equine dermis (ED) cells cell lines. We compared morphologic and biochemical features of early and late apoptosis at different postinfection times. We investigated translocation of phosphatidylserine to the cell surface, nuclear fragmentation and changes in the cytoskeleton using flow cytometry and annexin V/propidium iodide staining, DNA laddering, terminal deoxynucleotidyl transferase UTP nick-end labeling assay and immunofluorescence staining of cytokeratin 18 cleavage...
November 21, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29160935/oh-the-places-they-ll-go-a-survey-of-phytopathogen-effectors-and-their-host-targets
#13
Madiha Khan, Derek Seto, Rajagopal Subramaniam, Darrell Desveaux
Phytopathogens translocate effector proteins into plant cells where they sabotage the host cellular machinery to promote infection. An individual pathogen can translocate numerous distinct effectors during the infection process to target an array of host macromolecules (proteins, metabolites, DNA, etc…) and manipulate them using a variety of enzymatic activities. In this review, we have surveyed the literature for effector targets and curated them to convey the range of functions carried out by phytopathogenic proteins inside host cells...
November 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29160738/h4k20me2-distinguishes-pre-replicative-from-post-replicative-chromatin-to-appropriately-direct-dna-repair-pathway-choice-by-53bp1-rif1-mad2l2
#14
Marco Simonetta, Inge de Krijger, Judit Serrat, Nathalie Moatti, Diogo Fortunato, Liesbeth Hoekman, Onno B Bleijerveld, A F Maarten Altelaar, Jacqueline J L Jacobs
The main pathways for the repair of DNA double strand breaks (DSBs) are non-homologous end-joining (NHEJ) and homologous recombination directed repair (HDR). These operate mutually exclusive and are activated by 53BP1 and BRCA1, respectively. As HDR can only succeed in the presence of an intact copy of replicated DNA, cells employ several mechanisms to inactivate HDR in the G1 phase of cell cycle. As cells enter S-phase, these inhibitory mechanisms are released and HDR becomes active. However, during DNA replication, NHEJ and HDR pathways are both functional and non-replicated and replicated DNA regions co-exist, with the risk of aberrant HDR activity at DSBs in non-replicated DNA...
November 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29160417/radiotherapy-modulates-expression-of-egfr-ercc1-and-p53-in-cervical-cancer
#15
V H de Almeida, A C de Melo, D D Meira, A C Pires, A Nogueira-Rodrigues, H K Pimenta-Inada, F G Alves, G Moralez, L S Thiago, C G Ferreira, C Sternberg
Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry...
November 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29160308/programmable-base-editing-of-a%C3%A2-t-to-g%C3%A2-c-in-genomic-dna-without-dna-cleavage
#16
Nicole M Gaudelli, Alexis C Komor, Holly A Rees, Michael S Packer, Ahmed H Badran, David I Bryson, David R Liu
The spontaneous deamination of cytosine is a major source of C•G to T•A transitions, which account for half of known human pathogenic point mutations. The ability to efficiently convert target A•T base pairs to G•C could therefore advance the study and treatment of genetic diseases. While the deamination of adenine yields inosine, which is treated as guanine by polymerases, no enzymes are known to deaminate adenine in DNA. Here we report adenine base editors (ABEs) that mediate conversion of A•T to G•C in genomic DNA...
October 25, 2017: Nature
https://www.readbyqxmd.com/read/29160298/tdp2-top2-and-sumo-what-is-zatt-about
#17
Guido Zagnoli-Vieira, Keith W Caldecott
Recently, ZATT (also known as ZNF451 or Zpf451) was reported by Schellenberg et al. to aid the removal of Topoisomerase II cleavage complexes by stimulating the phosphodiesterase activity of Tyrosyl DNA Phosphodiesterase 2. Although the full implication of this discovery is unknown, it will help us understand how cells respond to topoisomerase-induced genome damage and chemotherapeutic topoisomerase 'poisons'.
November 21, 2017: Cell Research
https://www.readbyqxmd.com/read/29160297/structural-and-functional-analyses-of-the-mammalian-tin2-tpp1-trf2-telomeric-complex
#18
Chunyi Hu, Rekha Rai, Chenhui Huang, Cayla Broton, Juanjuan Long, Ying Xu, Jing Xue, Ming Lei, Sandy Chang, Yong Chen
Telomeres are nucleoprotein complexes that play essential roles in protecting chromosome ends. Mammalian telomeres consist of repetitive DNA sequences bound by the shelterin complex. In this complex, the POT1-TPP1 heterodimer binds to single-stranded telomeric DNAs, while TRF1 and TRF2-RAP1 interact with double-stranded telomeric DNAs. TIN2, the linchpin of this complex, simultaneously interacts with TRF1, TRF2, and TPP1 to mediate the stable assembly of the shelterin complex. However, the molecular mechanism by which TIN2 interacts with these proteins to orchestrate telomere protection remains poorly understood...
November 21, 2017: Cell Research
https://www.readbyqxmd.com/read/29160296/structure-of-the-fission-yeast-s-pombe-telomeric-tpz1-poz1-rap1-complex
#19
Jing Xue, Hongwen Chen, Jian Wu, Miho Takeuchi, Haruna Inoue, Yanmei Liu, Hong Sun, Yong Chen, Junko Kanoh, Ming Lei
Telomeric shelterin complex caps chromosome ends and plays a crucial role in telomere maintenance and protection. In the fission yeast Schizosaccharomyces pombe, shelterin is composed of telomeric single- and double-stranded DNA-binding protein subcomplexes Pot1-Tpz1 and Taz1-Rap1, which are bridged by their interacting protein Poz1. However, the structure of Poz1 and how Poz1 functions as an interaction hub in the shelterin complex remain unclear. Here we report the crystal structure of Poz1 in complex with Poz1-binding motifs of Tpz1 and Rap1...
November 21, 2017: Cell Research
https://www.readbyqxmd.com/read/29160201/aquicoccus-porphyridii-gen-nov-sp-nov-isolated-from-a-small-marine-red-alga-porphyridium-marinum
#20
Tingye Feng, Kyung Hyun Kim, Sang Eun Jeong, Wonyong Kim, Che Ok Jeon
A Gram-stain-negative, non-motile and aerobic bacterial strain, designated L1 8-17(T), was isolated from a marine alga, Porphyridium marinum, in South Korea. Cells of strain L1 8-17(T) were found to be oxidase- and catalase-positive cocci without flagella. Growth of strain L1 8-17(T) was observed at 20-40 °C (optimum, 37 °C), pH 6.0-10.0 (optimum, pH 7.0-8.0) and in the presence of 0-7 % (w/v) NaCl (optimum, 2-3 %). The isoprenoid quinone detected was only ubiquinone-10. Summed feature 8 (comprising C18 : 1ω7c/C18 : 1ω6c) and C16 : 0 were detected as major cellular fatty acids...
November 21, 2017: International Journal of Systematic and Evolutionary Microbiology
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