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https://www.readbyqxmd.com/read/28743002/drosophila-histone-demethylase-kdm4a-has-enzymatic-and-non-enzymatic-roles-in-controlling-heterochromatin-integrity
#1
Serafin U Colmenares, Joel M Swenson, Sasha A Langley, Cameron Kennedy, Sylvain V Costes, Gary H Karpen
Eukaryotic genomes are broadly divided between gene-rich euchromatin and the highly repetitive heterochromatin domain, which is enriched for proteins critical for genome stability and transcriptional silencing. This study shows that Drosophila KDM4A (dKDM4A), previously characterized as a euchromatic histone H3 K36 demethylase and transcriptional regulator, predominantly localizes to heterochromatin and regulates heterochromatin position-effect variegation (PEV), organization of repetitive DNAs, and DNA repair...
July 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28741503/the-pushmi-pullyu-of-dna-repair-clinical-synthetic-lethality
#2
REVIEW
S Percy Ivy, Johann de Bono, Elise C Kohn
Maintenance of genomic integrity is critical for adaptive survival in the face of endogenous and exogenous environmental stress. The loss of stability and fidelity in the genome caused by cancer and cancer treatment provides therapeutic opportunities to leverage the critical balance between DNA injury and repair. Blocking repair and pushing damaged DNA through the cell cycle using therapeutic inhibitors exemplify the 'pushmi-pullyu' effect of disrupted DNA repair. DNA repair inhibitors (DNARi) can be separated into five biofunctional categories: sensors, mediators, transducers, effectors, and collaborators that recognize DNA damage, propagate injury DNA messages, regulate cell cycle checkpoints, and alter the microenvironment...
November 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28740759/a-positive-readout-single-transcript-reporter-for-site-specific-mrna-cleavage
#3
Nikolay Kandul, Ming Guo, Bruce A Hay
Cleavage of mRNA molecules causes their rapid degradation, thereby playing an important role in regulation of gene expression and host genome defense from viruses and transposons in bacterial and eukaryotic cells. Current negative-readout, and repressor-based positive-readout reporters of mRNA degradation have limitations. Here we report the development of a single transcript that acts as a positive reporter of mRNA cleavage. We show that placement of bacterial CopT and CopA hairpins into the 5' UTR and 3' UTR of an mRNA results in inhibition of translation of the intervening coding sequence in Drosophila...
2017: PeerJ
https://www.readbyqxmd.com/read/28738244/dna-binding-and-unwinding-by-hel308-helicase-requires-dual-functions-of-a-winged-helix-domain
#4
Sarah J Northall, Ryan Buckley, Nathan Jones, J Carlos Penedo, Panos Soultanas, Edward L Bolt
Hel308 helicases promote genome stability linked to DNA replication in archaea, and have homologues in metazoans. In the crystal structure of archaeal Hel308 bound to a tailed DNA duplex, core helicase domains encircle single-stranded DNA (ssDNA) in a "ratchet" for directional translocation. A winged helix domain (WHD) is also present, but its function is mysterious. We investigated the WHD in full-length Hel308, identifying that mutations in a solvent exposed α-helix resulted in reduced DNA binding and unwinding activities...
July 16, 2017: DNA Repair
https://www.readbyqxmd.com/read/28737169/actomyosin-drives-cancer-cell-nuclear-dysmorphia-and-threatens-genome-stability
#5
Tohru Takaki, Marco Montagner, Murielle P Serres, Maël Le Berre, Matt Russell, Lucy Collinson, Karoly Szuhai, Michael Howell, Simon J Boulton, Erik Sahai, Mark Petronczki
Altered nuclear shape is a defining feature of cancer cells. The mechanisms underlying nuclear dysmorphia in cancer remain poorly understood. Here we identify PPP1R12A and PPP1CB, two subunits of the myosin phosphatase complex that antagonizes actomyosin contractility, as proteins safeguarding nuclear integrity. Loss of PPP1R12A or PPP1CB causes nuclear fragmentation, nuclear envelope rupture, nuclear compartment breakdown and genome instability. Pharmacological or genetic inhibition of actomyosin contractility restores nuclear architecture and genome integrity in cells lacking PPP1R12A or PPP1CB...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28735897/radx-promotes-genome-stability-and-modulates-chemosensitivity-by-regulating-rad51-at-replication-forks
#6
Huzefa Dungrawala, Kamakoti P Bhat, Rémy Le Meur, Walter J Chazin, Xia Ding, Shyam K Sharan, Sarah R Wessel, Aditya A Sathe, Runxiang Zhao, David Cortez
RAD51 promotes homology-directed repair (HDR), replication fork reversal, and stalled fork protection. Defects in these functions cause genomic instability and tumorigenesis but also generate hypersensitivity to cancer therapeutics. Here we describe the identification of RADX as an RPA-like, single-strand DNA binding protein. RADX is recruited to replication forks, where it prevents fork collapse by regulating RAD51. When RADX is inactivated, excessive RAD51 activity slows replication elongation and causes double-strand breaks...
July 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28733817/enriching-an-intraspecific-genetic-map-and-identifying-qtl-for-fiber-quality-and-yield-component-traits-across-multiple-environments-in-upland-cotton-gossypium-hirsutum-l
#7
Xueying Liu, Zhonghua Teng, Jinxia Wang, Tiantian Wu, Zhiqin Zhang, Xianping Deng, Xiaomei Fang, Zhaoyun Tan, Iftikhar Ali, Dexin Liu, Jian Zhang, Dajun Liu, Fang Liu, Zhengsheng Zhang
Cotton is a significant commercial crop that plays an indispensable role in many domains. Constructing high-density genetic maps and identifying stable quantitative trait locus (QTL) controlling agronomic traits are necessary prerequisites for marker-assisted selection (MAS). A total of 14,899 SSR primer pairs designed from the genome sequence of G. raimondii were screened for polymorphic markers between mapping parents CCRI 35 and Yumian 1, and 712 SSR markers showing polymorphism were used to genotype 180 lines from a (CCRI 35 × Yumian 1) recombinant inbred line (RIL) population...
July 21, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28733408/dna-double-strand-break-repair-assay
#8
Chen-Chun Pai, Elizabeth Blaikley, Timothy C Humphrey
DNA double-strand breaks (DSBs), arising during normal DNA metabolism or following exposure to mutagenic agents such as ionizing radiation can lead to chromosomal rearrangements and genome instability, and are potentially lethal if unrepaired. Therefore, understanding the mechanisms of DSB repair and misrepair, and identifying the factors involved in these processes is of biological as well as medical interest. Here we describe a DSB assay in Schizosaccharomyces pombe that can be used to identify and quantify different repair, misrepair, and failed repair events resulting from a site-specific DSB within the context of a nonessential minichromosome, Ch(16) This assay can be used to determine the contribution of most genes or genetic backgrounds to DSB repair and genome stability, and can also provide mechanistic insights into their function...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28733402/analysis-of-dna-metabolism-in-fission-yeast
#9
Francisco Antequera, Timothy C Humphrey
The fission yeast Schizosaccharomyces pombe is an excellent model organism to study DNA metabolism, in which the DNA replication and repair mechanisms are evolutionarily conserved. In this introduction we describe a range of methods commonly used to study aspects of DNA metabolism in fission yeast, focusing on approaches used for the analysis of genome stability, DNA replication, and DNA repair. We describe the use of a minichromosome, Ch(16), for monitoring different aspects of genome stability. We introduce two-dimensional gel electrophoresis and immunofluorescent visualization of combed DNA molecules for the analysis of DNA replication...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28732184/high-throughput-identification-of-mir-596-inducing-p53-mediated-apoptosis-in-hela-and-hct116-cells-using-cell-microarray
#10
Ming Ma, Junyu Yang, Bolun Wang, Zhihua Zhao, Jianzhong Jeff Xi
miRNAs play a key role in the regulation of gene networks in mammalian cells. However, little is known about their roles and functions in the apoptosis pathway. Here, we conducted a whole-genome miRNA screening for apoptosis and identified more than 100 miRNAs as apoptosis inducers. To further explain the roles of these mRNAs in apoptosis, a second round of screening was conducted between p53 +/+ and -/- cells. Among the hits, miR-596 was identified as a regulator of p53. The overexpression of miR-596 significantly increased p53 at the protein level, thereby inducing apoptosis...
July 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28731643/transcriptome-based-identification-of-the-optimal-reference-cho-genes-for-normalisation-of-qpcr-data
#11
Adam J Brown, Suzanne Gibson, Diane Hatton, David C James
Real-time quantitative PCR (qPCR) is the standard method for determination of relative changes in mRNA transcript abundance. Analytical accuracy, precision, and reliability are critically dependent on the selection of internal control reference genes. In this study we have identified optimal reference genes that can be utilized universally for qPCR analysis of CHO cell mRNAs. Initially, transcriptomic datasets were analysed to identify eight endogenous genes that exhibited high expression stability across four distinct CHO cell lines sampled in different culture phases...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28730763/dna-mismatch-repair-deficiency-in-lung-and-oral-cavity-carcinomas-the-role-of-histogenetic-origin
#12
Konstantina N Spetsotaki, Evangelos Tsiambas, Athanasios Stamatelopoulos, Panagiotis P Fotiades, Ioannis Kastanioudakis, Pericles Tomos, Vasileios Ragos
DNA mismatch repair system (DNA MMR) is a crucial genetic mechanism for DNA homeostasis in prokaryotic and eukaryotic cells. During DNA replication and also recombination, point intra-nucleotide errors including base deletion, insertion, and mis-incorporation happen. These raised abnormalities in the newly synthesized DNA strand could affect negatively the stability of the molecule and the function of the corresponding genes. DNA MMR proteins prevent these errors by recognizing and repairing them, securing directly the normal anatomy of the DNA double strand and indirectly the expression of the genes...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28730334/mir-181a-2-downregulates-the-e3-ubiquitin-ligase-cul4a-transcript-and-promotes-cell-proliferation
#13
Venkateshwarlu Bandi, Sudhakar Baluchamy
MiR-181a-2 plays a major role in cell proliferation both positively and negatively depending on tissue type by targeting several regulators 3'UTR regions. We have predicted several targets for miR-181a-2 through computational approaches and characterized one its interesting target, CUL4A, an E3 ubiquitin ligase. CUL4A regulates diverse functions in the cells including DNA repair, DNA replication, cell cycle, genomic stability through polyubiquitination of target proteins. Deregulation of both miR-181a-2 and CUL4A are reported in many cancerous cells, but the functional link between them is unknown...
August 2017: Medical Oncology
https://www.readbyqxmd.com/read/28729824/mouse-models-of-c9orf72-hexanucleotide-repeat-expansion-in-amyotrophic-lateral-sclerosis-frontotemporal-dementia
#14
REVIEW
Ranjan Batra, Chris W Lee
The presence of hexanucleotide repeat expansion (HRE) in the first intron of the human C9orf72 gene is the most common genetic cause underlying both familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies aimed at elucidating the pathogenic mechanisms associated of C9orf72 FTD and ALS (C9FTD/ALS) have focused on the hypothesis of RNA and protein toxic gain-of-function models, including formation of nuclear RNA foci containing GGGGCC (G4C2) HRE, inclusions containing dipeptide repeat proteins through a non-canonical repeat associated non-ATG (RAN) translation mechanism, and on loss-of-function of the C9orf72 protein...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28728980/the-role-of-hexon-protein-as-a-molecular-mold-in-patterning-the-protein-ix-organization-in-human-adenoviruses
#15
Vijay S Reddy
Adenoviruses are respiratory, ocular and enteric pathogens that form complex capsids, which are assembled from seven different structural proteins and composed of several core proteins that closely interact with the packaged dsDNA genome. The recent near-atomic resolution structures revealed that the interlacing continuous hexagonal network formed by the protein IX (IX) molecules is conserved among different human adenoviruses (HAdVs), but not in non-human adenoviruses (non-HAdVs). In this report we propose a distinct role for the hexon protein as a "molecular mold" in enabling the formation of such hexagonal IX-network that has been shown to preserve the stability, infectivity of HAdVs...
July 17, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28724762/stability-of-cucumber-necrosis-virus-at-the-quasi-six-fold-axis-affects-zoospore-transmission
#16
Michael B Sherman, Kishore Kakani, D'Ann Rochon, Wen Jiang, Neil R Voss, Thomas J Smith
Cucumber necrosis virus (CNV) is a member of the genus Tombusvirus and has a monopartite positive-sense RNA genome. CNV is transmitted in nature via zoospores of the fungus, Olpidium bornovanus As with other members of the Tombusvirus genus, the CNV capsid swells when exposed to alkaline pH and EDTA. We previously demonstrated that a P73G mutation blocks the virus from zoospore transmission while not significantly affecting replication in plants (1). P73 lies immediately adjacent to a putative zinc binding site (2) that is formed by three icosahedrally related His residues in the N-termini of the C subunit at the quasi 6-fold axes...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724062/increasing-genomic-enabled-prediction-accuracy-by-modeling-genotype-%C3%A3-environment-interactions-in-kansas-wheat
#17
Diego Jarquín, Cristiano Lemes da Silva, R Chris Gaynor, Jesse Poland, Allan Fritz, Reka Howard, Sarah Battenfield, Jose Crossa
Wheat ( L.) breeding programs test experimental lines in multiple locations over multiple years to get an accurate assessment of grain yield and yield stability. Selections in early generations of the breeding pipeline are based on information from only one or few locations and thus materials are advanced with little knowledge of the genotype × environment interaction (G × E) effects. Later, large trials are conducted in several locations to assess the performance of more advanced lines across environments...
July 2017: Plant Genome
https://www.readbyqxmd.com/read/28723273/the-repair-project-examining-the-biological-impacts-of-sub-background-radiation-exposure-within-snolab-a-deep-underground-laboratory
#18
Christopher Thome, Sujeenthar Tharmalingam, Jake Pirkkanen, Andrew Zarnke, Taylor Laframboise, Douglas R Boreham
Considerable attention has been given to understanding the biological effects of low-dose ionizing radiation exposure at levels slightly above background. However, relatively few studies have been performed to examine the inverse, where natural background radiation is removed. The limited available data suggest that organisms exposed to sub-background radiation environments undergo reduced growth and an impaired capacity to repair genetic damage. Shielding from background radiation is inherently difficult due to high-energy cosmic radiation...
July 19, 2017: Radiation Research
https://www.readbyqxmd.com/read/28723239/disruption-of-cdk-resistant-chromatin-association-by-prb-causes-dna-damage-mitotic-errors-and-reduces-condensin-ii-recruitment
#19
Charles A Ishak, Courtney H Coschi, Michael V Roes, Frederick A Dick
Organization of chromatin structure is indispensible to the maintenance of genome integrity. The retinoblastoma tumor suppressor protein (pRB) mediates both transcriptional repression and chromatin organization, but the independent contributions of these functions have been difficult to study. Here, we utilize a synthetic Rb1 mutant allele (F832A) that maintains pRB association at cell cycle gene promoters, but disrupts a cyclin-dependent kinase (CDK)-resistant interaction with E2F1 to reduce occupancy of pRB on intergenic chromatin...
July 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28720801/mapping-and-characterization-of-g-quadruplexes-in-mycobacterium-tuberculosis-gene-promoter-regions
#20
Rosalba Perrone, Enrico Lavezzo, Erika Riello, Riccardo Manganelli, Giorgio Palù, Stefano Toppo, Roberta Provvedi, Sara N Richter
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites...
July 18, 2017: Scientific Reports
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