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https://www.readbyqxmd.com/read/28518146/acyl-coa-thioesterase-7-is-involved-in-cell-cycle-progression-via-regulation-of-pkc%C3%AE-p53-p21-signaling-pathway
#1
Seung Hee Jung, Hyung Chul Lee, Hyun Jung Hwang, Hyun A Park, Young-Ah Moon, Bong Cho Kim, Hyeong Min Lee, Kwang Pyo Kim, Yong-Nyun Kim, Byung Lan Lee, Jae Cheol Lee, Young-Gyu Ko, Heon Joo Park, Jae-Seon Lee
Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that catalyzes hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. However, canonical and non-canonical functions of ACOT7 remain to be discovered. In this study, for the first time, ACOT7 was shown to be responsive to genotoxic stresses such as ionizing radiation (IR) and the anti-cancer drug doxorubicin in time- and dose-dependent manners. ACOT7 knockdown induced cytostasis via activation of the p53-p21 signaling pathway without a DNA damage response...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28506636/multiple-dna-interactions-contribute-to-the-initiation-of-telomerase-elongation
#2
Ahu Karademir Andersson, Cecilia Gustafsson, Roopesh Krishnankutty, Marita Cohn
Telomerase maintains telomere length and chromosome integrity by adding short tandem repeats of single-stranded DNA to the 3' ends, via reverse transcription of a defined template region of its RNA subunit. To further understand the telomerase elongation mechanism, we studied the primer utilization and extension activity of the telomerase from the budding yeast Naumovozyma castellii (Saccharomyces castellii), which displays a processive nucleotide and repeat addition polymerization. For the efficient initiation of canonical elongation, telomerase required 4nt primer 3' end complementarity to the template RNA...
May 12, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28505197/structure-of-ca2-binding-protein-6-from-entamoeba-histolytica-and-its-involvement-in-trophozoite-proliferation-regulation
#3
Deepshikha Verma, Aruna Murmu, Samudrala Gourinath, Alok Bhattacharya, Kandala V R Chary
Cell cycle of Entamoeba histolytica, the etiological agent of amoebiasis, follows a novel pathway, which includes nuclear division without the nuclear membrane disassembly. We report a nuclear localized Ca2+-binding protein from E. histolytica (abbreviated hereafter as EhCaBP6), which is associated with microtubules. We determined the 3D solution NMR structure of EhCaBP6, and identified one unusual, one canonical and two non-canonical cryptic EF-hand motifs. The cryptic EF-II and EF-IV pair with the Ca2+-binding EF-I and EF-III, respectively, to form a two-domain structure similar to Calmodulin and Centrin proteins...
May 15, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28497172/deep-intronic-mutations-and-human-disease
#4
REVIEW
Rita Vaz-Drago, Noélia Custódio, Maria Carmo-Fonseca
Next-generation sequencing has revolutionized clinical diagnostic testing. Yet, for a substantial proportion of patients, sequence information restricted to exons and exon-intron boundaries fails to identify the genetic cause of the disease. Here we review evidence from mRNA analysis and entire genomic sequencing indicating that pathogenic mutations can occur deep within the introns of over 75 disease-associated genes. Deleterious DNA variants located more than 100 base pairs away from exon-intron junctions most commonly lead to pseudo-exon inclusion due to activation of non-canonical splice sites or changes in splicing regulatory elements...
May 12, 2017: Human Genetics
https://www.readbyqxmd.com/read/28482831/molecular-dynamics-simulation-of-the-opposite-base-preference-and-interactions-in-the-active-site-of-formamidopyrimidine-dna-glycosylase
#5
Alexander V Popov, Anton V Endutkin, Yuri N Vorobjev, Dmitry O Zharkov
BACKGROUND: Formamidopyrimidine-DNA glycosylase (Fpg) removes abundant pre-mutagenic 8-oxoguanine (oxoG) bases from DNA through nucleophilic attack of its N-terminal proline at C1' of the damaged nucleotide. Since oxoG efficiently pairs with both C and A, Fpg must excise oxoG from pairs with C but not with A, otherwise a mutation occurs. The crystal structures of several Fpg-DNA complexes have been solved, yet no structure with A opposite the lesion is available. RESULTS: Here we use molecular dynamic simulation to model interactions in the pre-catalytic complex of Lactococcus lactis Fpg with DNA containing oxoG opposite C or A, the latter in either syn or anti conformation...
May 8, 2017: BMC Structural Biology
https://www.readbyqxmd.com/read/28469731/integrated-data-analysis-reveals-potential-drivers-and-pathways-disrupted-by-dna-methylation-in-papillary-thyroid-carcinomas
#6
Caroline Moraes Beltrami, Mariana Bisarro Dos Reis, Mateus Camargo Barros-Filho, Fabio Albuquerque Marchi, Hellen Kuasne, Clóvis Antônio Lopes Pinto, Srikant Ambatipudi, Zdenko Herceg, Luiz Paulo Kowalski, Silvia Regina Rogatto
BACKGROUND: Papillary thyroid carcinoma (PTC) is a common endocrine neoplasm with a recent increase in incidence in many countries. Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified. In this study, DNA methylation profile (Illumina HumanMethylation 450K) of 41 PTC paired with non-neoplastic adjacent tissues (NT) was carried out to identify and contribute to the elucidation of the role of novel genic and intergenic regions beyond those described in the promoter and CpG islands (CGI)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28469639/telomerase-and-mtor-in-the-brain-the-mitochondria-connection
#7
REVIEW
Satomi Miwa, Gabriele Saretzki
Telomerase is an enzyme that maintains telomeres in dividing cells using a template on its inherent RNA component. Additionally, the protein part TERT (Telomerase Reverse Transcriptase) has various non-canonical functions. For example, it can localize to mitochondria under increased stress and protect cells in vitro from oxidative stress, DNA damage and apoptosis. Recently it has been demonstrated that TERT protein persists in adult neurons in the brain and data emerge suggesting that it might have a protective function in these post-mitotic cells as well...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28464292/rnai-mediated-gene-silencing-of-itpa-using-a-targeted-nanocarrier-apoptosis-induction-in-skbr3-cancer-cells
#8
Fahimeh Charbgoo, Mehrdad Behmanesh, Maryam Nikkhah, Eric G Kane
A pure nucleotide pool is required for high-fidelity DNA replication and prevention of carcinogenesis in living cells. Human inosine triphosphatase (ITPase), encoded by the ITPA gene, plays a critical role in maintaining the purity of the cellular nucleotide pool by excluding nucleotides that enhance mutagenesis. ITPase is a nucleoside triphosphate pyrophosphatase that hydrolyzes the non-canonical nucleotides inosine triphosphate (ITP) and xanthine triphosphate (XTP). The monophosphate products of ITPase reactions are subsequently excluded from the nucleotide pool and the improper substitution of ITP and XTP into DNA and RNA is prevented...
May 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28460268/pol%C3%AE-deficiency-induces-moderate-shortening-of-p53-mouse-lifespan-and-modifies-tumor-spectrum
#9
Beatriz Escudero, Diego Herrero, Yaima Torres, Susana Cañón, Antonio Molina, Rosa M Carmona, Javier Suela, Luis Blanco, Enrique Samper, Antonio Bernad
Non-homologous end joining (NHEJ) is the main mechanism for double strand break (DSB) DNA repair. The error-prone DNA polymerase mu (Polμ) is involved in immunoglobulin variable region rearrangement and in general, NHEJ in non-lymphoid cells. Deletion of NHEJ factors in P53(-/-) mice, which are highly prone to development of T cell lymphoma, generally increases cancer incidence and shifts the tumor spectrum towards aggressive pro-B lymphoma. In contrast, Polμ deletion increased sarcoma incidence, proportionally reducing pro-B lymphoma development on the P53-deficient background...
April 10, 2017: DNA Repair
https://www.readbyqxmd.com/read/28456604/herpesviruses-hijack-host-exosomes-for-viral-pathogenesis
#10
REVIEW
Sara Sadeghipour, Rommel A Mathias
Herpesviruses are remarkable pathogens possessing elaborate mechanisms to seize various host cellular components for immune evasion, replication, and virion egress. As viruses are dependent upon their hosts, investigating this intricate interplay has revealed that the exosome pathway is utilised by alpha (Herpes Simplex Virus 1), beta (Human Cytomegalovirus, and Human Herpesvirus 6) and gamma (Epstein-Barr Virus, and Kaposi Sarcoma-associated Herpesvirus) herpesviruses. Virions and exosomes share similar properties and functions...
April 26, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28418376/a-circrna-from-sepallata3-regulates-splicing-of-its-cognate-mrna-through-r-loop-formation
#11
Vanessa M Conn, Véronique Hugouvieux, Aditya Nayak, Stephanie A Conos, Giovanna Capovilla, Gökhan Cildir, Agnès Jourdain, Vinay Tergaonkar, Markus Schmid, Chloe Zubieta, Simon J Conn
Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life(1), yet their functions have remained elusive. Here, we report that circRNAs can be used as bona fide biomarkers of functional, exon-skipped AS variants in Arabidopsis, including in the homeotic MADS-box transcription factor family...
April 18, 2017: Nature Plants
https://www.readbyqxmd.com/read/28416970/dna-methylation-profiling-in-peripheral-lung-tissues-of-smokers-and-patients-with-copd
#12
Isaac K Sundar, Qiangzong Yin, Brian S Baier, Li Yan, Witold Mazur, Dongmei Li, Martha Susiarjo, Irfan Rahman
BACKGROUND: Epigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers. We isolated DNA from parenchymal lung tissues of patients including eight lifelong non-smokers, eight current smokers, and eight patients with COPD and analyzed the samples using Illumina's Infinium HumanMethylation450 BeadChip...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28412515/genome-wide-determination-of-transcription-start-sites-reveals-new-insights-into-promoter-structures-in-the-actinomycete-corynebacterium-glutamicum
#13
Andreas Albersmeier, Katharina Pfeifer-Sancar, Christian Rückert, Jörn Kalinowski
The genome-wide identification of transcription start sites, enabled by high-throughput sequencing of a cDNA library enriched for native 5' transcript ends, is ideally suited for the analysis of promoters. Here, the transcriptome of Corynebacterium glutamicum, a non-pathogenic soil bacterium from the actinomycetes branch that is used in industry for the production of amino acids, was analysed by transcriptome sequencing of the 5'-ends of native transcripts. Total RNA samples were harvested from the exponential phase of growth, therefore the study mainly addressed promoters recognized by the main house-keeping sigma factor σ(A)...
April 13, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28406751/repetitive-dna-loci-and-their-modulation-by-the-non-canonical-nucleic-acid-structures-r-loops-and-g-quadruplexes
#14
REVIEW
Amanda C Hall, Lauren A Ostrowski, Violena Pietrobon, Karim Mekhail
Cells have evolved intricate mechanisms to maintain genome stability despite allowing mutational changes to drive evolutionary adaptation. Repetitive DNA sequences, which represent the bulk of most genomes, are a major threat to genome stability often driving chromosome rearrangements and disease. The major source of repetitive DNA sequences and thus the most vulnerable constituents of the genome are the rDNA (rDNA) repeats, telomeres, and transposable elements. Maintaining the stability of these loci is critical to overall cellular fitness and lifespan...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28402520/a-non-canonical-multisubunit-rna-polymerase-encoded-by-the-ar9-phage-recognizes-the-template-strand-of-its-uracil-containing-promoters
#15
Maria Sokolova, Sergei Borukhov, Daria Lavysh, Tatjana Artamonova, Mikhail Khodorkovskii, Konstantin Severinov
AR9 is a giant Bacillus subtilis phage whose uracil-containing double-stranded DNA genome encodes distant homologs of β and β' subunits of bacterial RNA polymerase (RNAP). The products of these genes are thought to assemble into two non-canonical multisubunit RNAPs - a virion RNAP (vRNAP) that is injected into the host along with phage DNA to transcribe early phage genes, and a non-virion RNAP (nvRNAP), which is synthesized during the infection and transcribes late phage genes. We purified the AR9 nvRNAP from infected B...
April 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28398238/ltr-retrotransposons-from-bdelloid-rotifers-capture-additional-orfs-shared-between-highly-diverse-retroelement-types
#16
Fernando Rodriguez, Aubrey W Kenefick, Irina R Arkhipova
Rotifers of the class Bdelloidea, microscopic freshwater invertebrates, possess a highlydiversified repertoire of transposon families, which, however, occupy less than 4% of genomic DNA in the sequenced representative Adineta vaga. We performed a comprehensive analysis of A. vaga retroelements, and found that bdelloid long terminal repeat (LTR)retrotransposons, in addition to conserved open reading frame (ORF) 1 and ORF2 corresponding to gag and pol genes, code for an unusually high variety of ORF3 sequences...
April 11, 2017: Viruses
https://www.readbyqxmd.com/read/28390866/activation-of-transforming-growth-factor-beta-1-signaling-in-gastric-cancer-associated-fibroblasts-increases-their-motility-via-expression-of-rhomboid-5-homolog-2-and-ability-to-induce-invasiveness-of-gastric-cancer-cells
#17
Takatsugu Ishimoto, Keisuke Miyake, Tannistha Nandi, Masakazu Yashiro, Nobuyuki Onishi, Kie Kyon Huang, Suling Joyce Lin, Ramnarayanan Kalpana, Su Ting Tay, Yuka Suzuki, Byoung Chul Cho, Daisuke Kuroda, Kota Arima, Daisuke Izumi, Masaaki Iwatsuki, Yoshifumi Baba, Eiji Oki, Masayuki Watanabe, Hideyuki Saya, Kosei Hirakawa, Hideo Baba, Patrick Tan
BACKGROUND & AIMS: Fibroblasts that interact with cancer cells are called cancer-associated fibroblasts (CAFs)-they promote progression of different tumor types. We investigated the characteristics and functions of CAFs in diffuse-type gastric cancers (DGCs) by analyzing features of their genome and gene expression patterns. METHODS: We isolated CAFs and adjacent non-cancer fibroblasts (NFs) from 110 GC tissues from patients who underwent gastrectomy in Japan from 2008 through 2016...
April 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28382477/rna-g-quadruplexes-as-key-motifs-of-the-transcriptome
#18
Samuel Rouleau, Rachel Jodoin, Jean-Michel Garant, Jean-Pierre Perreault
G-Quadruplexes are non-canonical secondary structures that can be adopted under physiological conditions by guanine-rich DNA and RNA molecules. They have been reported to occur, and to perform multiple biological functions, in the genomes and transcriptomes of many species, including humans. This chapter focuses specifically on RNA G-quadruplexes and reviews the most recent discoveries in the field, as well as addresses the upcoming challenges researchers studying these structures face.
April 6, 2017: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/28378742/fancd2-in-vivo-interaction-network-reveals-a-non-canonical-role-in-mitochondrial-function
#19
Tingting Zhang, Wei Du, Andrew F Wilson, Satoshi H Namekawa, Paul R Andreassen, Amom Ruhikanta Meetei, Qishen Pang
Fancd2 is a component of the Fanconi anemia (FA) DNA repair pathway, which is frequently found defective in human cancers. The full repertoire of Fancd2 functions in normal development and tumorigenesis remains to be determined. Here we developed a Flag- and hemagglutinin-tagged Fancd2 knock-in mouse strain that allowed a high throughput mass spectrometry approach to search for Fancd2-binding proteins in different mouse organs. In addition to DNA repair partners, we observed that many Fancd2-interacting proteins are mitochondrion-specific...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28376558/pfap2tel-harbouring-a-non-canonical-dna-binding-ap2-domain-binds-to-plasmodium-falciparum-telomeres
#20
Miguel Sierra-Miranda, Shruthi-Sridhar Vembar, Dulce María Delgadillo, Pedro A Ávila-López, Abril-Marcela Herrera-Solorio, Daniela Lozano Amado, Miguel Vargas, Rosaura Hernandez-Rivas
The telomeres of the malaria parasite Plasmodium falciparum are essential not only for chromosome end maintenance during blood stage development in humans but also to generate genetic diversity by facilitating homologous recombination of subtelomeric, multigene virulence families such as var and rifin. However, other than the telomerase PfTERT, proteins that act at P. falciparum telomeres are poorly characterised. To isolate components that bind to telomeres, we performed oligonucleotide pulldowns and electromobility shift assays with a telomeric DNA probe and identified a non-canonical member of the ApiAP2 family of transcription factors, PfAP2Tel (encoded by PF3D7_0622900), as a component of the P...
April 4, 2017: Cellular Microbiology
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