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Elegans dna damage

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https://www.readbyqxmd.com/read/27874324/interaction-between-radioadaptive-response-and-radiation-induced-bystander-effect-in-caenorhabditis-elegans-a-unique-role-of-the-dna-damage-checkpoint
#1
Huangqi Tang, Liangwen Chen, Lianyun Chen, Bin Chen, Ting Wang, Aifeng Yang, Furu Zhan, Lijun Wu, Po Bian
Although radioadaptive responses (RAR) and radiation-induced bystander effects (RIBE) are two important biological effects of low-dose radiation, there are currently only limited data that directly address their interaction, particularly in the context of whole organisms. In previous studies, we separately demonstrated RAR and RIBE using an in vivo system of C. elegans . In the current study, we further investigated their interaction in C. elegans , with the ratio of protruding vulva as the biological end point for RAR...
November 22, 2016: Radiation Research
https://www.readbyqxmd.com/read/27831827/mitotic-entry-the-interplay-between-cdk1-plk1-and-bora
#2
Alfonso Parrilla, Luca Cirillo, Yann Thomas, Monica Gotta, Lionel Pintard, Anna Santamaria
Polo-like kinase 1 (Plk1) is an important mitotic kinase that is crucial for entry into mitosis after recovery from DNA damage-induced cell cycle arrest. Plk1 activation is promoted by the conserved protein Bora (SPAT-1 in C. elegans), which stimulates the phosphorylation of a conserved residue in the activation loop by the Aurora A kinase. In a recent article published in Cell Reports, we show that the master mitotic kinase Cdk1 contributes to Plk1 activation through SPAT-1/Bora phosphorylation. We identified 3 conserved Sp/Tp residues that are located in the N-terminal, most conserved part, of SPAT-1/Bora...
November 10, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27803194/quantification-of-in-vivo-progenitor-mutation-accrual-with-ultra-low-error-rate-and-minimal-input-dna-using-sip-hava-seq
#3
Pete H Taylor, Amanda Cinquin, Olivier Cinquin
Assaying in vivo accrual of DNA damage and DNA mutations by stem cells and pinpointing sources of damage and mutations would further our understanding of aging and carcinogenesis. Two main hurdles must be overcome. First, in vivo mutation rates are orders of magnitude lower than raw sequencing error rates. Second, stem cells are vastly outnumbered by differentiated cells, which have a higher mutation rate-quantification of stem cell DNA damage and DNA mutations is thus best performed from small, well-defined cell populations...
November 2016: Genome Research
https://www.readbyqxmd.com/read/27791127/cockayne-syndrome-group-a-and-b-proteins-converge-on-transcription-linked-resolution-of-non-b-dna
#4
Morten Scheibye-Knudsen, Anne Tseng, Martin Borch Jensen, Karsten Scheibye-Alsing, Evandro Fei Fang, Teruaki Iyama, Sanjay Kumar Bharti, Krisztina Marosi, Lynn Froetscher, Henok Kassahun, David Mark Eckley, Robert W Maul, Paul Bastian, Supriyo De, Soumita Ghosh, Hilde Nilsen, Ilya G Goldberg, Mark P Mattson, David M Wilson, Robert M Brosh, Myriam Gorospe, Vilhelm A Bohr
Cockayne syndrome is a neurodegenerative accelerated aging disorder caused by mutations in the CSA or CSB genes. Although the pathogenesis of Cockayne syndrome has remained elusive, recent work implicates mitochondrial dysfunction in the disease progression. Here, we present evidence that loss of CSA or CSB in a neuroblastoma cell line converges on mitochondrial dysfunction caused by defects in ribosomal DNA transcription and activation of the DNA damage sensor poly-ADP ribose polymerase 1 (PARP1). Indeed, inhibition of ribosomal DNA transcription leads to mitochondrial dysfunction in a number of cell lines...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27786254/a-novel-approach-using-c-elegans-dna-damage-induced-apoptosis-to-characterize-the-dynamics-of-uptake-transporters-for-therapeutic-drug-discoveries
#5
Arturo Papaluca, Dindial Ramotar
Organic cation transporter (OCT) function is critical for cellular homeostasis. C. elegans lacking OCT-1 displays a shortened lifespan and increased susceptibility to oxidative stress. We show that these phenotypes can be rescued by downregulating the OCT-1 paralogue, OCT-2. Herein, we delineate a biochemical pathway in C. elegans where uptake of genotoxic chemotherapeutics such as doxorubicin and cisplatin, and subsequent DNA damage-induced apoptosis of germ cells, are dependent exclusively upon OCT-2. We characterized OCT-2 as the main uptake transporter for doxorubicin, as well as a number of other therapeutic agents and chemical compounds, some identified through ligand-protein docking analyses...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27755535/genomic-scars-generated-by-polymerase-theta-reveal-the-versatile-mechanism-of-alternative-end-joining
#6
Robin van Schendel, Jane van Heteren, Richard Welten, Marcel Tijsterman
For more than half a century, genotoxic agents have been used to induce mutations in the genome of model organisms to establish genotype-phenotype relationships. While inaccurate replication across damaged bases can explain the formation of single nucleotide variants, it remained unknown how DNA damage induces more severe genomic alterations. Here, we demonstrate for two of the most widely used mutagens, i.e. ethyl methanesulfonate (EMS) and photo-activated trimethylpsoralen (UV/TMP), that deletion mutagenesis is the result of polymerase Theta (POLQ)-mediated end joining (TMEJ) of double strand breaks (DSBs)...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27718356/a-widely-employed-germ-cell-marker-is-an-ancient-disordered-protein-with-reproductive-functions-in-diverse-eukaryotes
#7
Michelle A Carmell, Gregoriy A Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C van Wolfswinkel, Kyomi J Igarashi, Daniel W Bellott, Michael Nefedov, Peter W Reddien, George C Enders, Vladimir N Uversky, Craig C Mello, David C Page
The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals...
October 8, 2016: ELife
https://www.readbyqxmd.com/read/27687175/dna-damage-responses-and-stress-resistance-concepts-from-bacterial-sos-to-metazoan-immunity
#8
Ashley B Williams, Björn Schumacher
The critical need for species preservation has driven the evolution of mechanisms that integrate stress signals from both exogenous and endogenous sources. Past research has been largely focused on cell-autonomous stress responses; however, recently their systemic outcomes within an organism and their implications at the ecological and species levels have emerged. Maintenance of species depends on the high fidelity transmission of the genome over infinite generations; thus, many pathways exist to monitor and restore the integrity of the genome and to coordinate DNA repair with other cellular processes, such as cell division and growth...
September 26, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27669387/toxicity-of-2-6-dichloro-1-4-benzoquinone-and-five-regulated-drinking-water-disinfection-by-products-for-the-caenorhabditis-elegans-nematode
#9
Yu-Ting Zuo, Yu Hu, Wei-Wei Lu, Jing-Jing Cao, Fan Wang, Xue Han, Wen-Qing Lu, Ai-Lin Liu
Scarce toxicological data are available for 2,6-dichloro-1,4-benzoquinone (DCBQ), an emerging water disinfection by-product (DBP) that is of potential public health concern. This study investigated the effects of DCBQ on the lethality, respiration rate, and DNA damage in the Caenorhabditis elegans nematode. Meanwhile, the toxic effects of five regulated DBPs, dichloroacetic acid (DCA), trichloroacetic acid (TCA), monobromoacetic acid (MBA), dibromoacetic acid (DBA), and N-nitrosodimethylamine (NDMA), have also been evaluated...
September 17, 2016: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/27669035/e4-ligase-specific-ubiquitination-hubs-coordinate-dna-double-strand-break-repair-and-apoptosis
#10
Leena Ackermann, Michael Schell, Wojciech Pokrzywa, Éva Kevei, Anton Gartner, Björn Schumacher, Thorsten Hoppe
Multiple protein ubiquitination events at DNA double-strand breaks (DSBs) regulate damage recognition, signaling and repair. It has remained poorly understood how the repair process of DSBs is coordinated with the apoptotic response. Here, we identified the E4 ubiquitin ligase UFD-2 as a mediator of DNA-damage-induced apoptosis in a genetic screen in Caenorhabditis elegans. We found that, after initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome...
September 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27668659/histone-h3k9-methylation-is-dispensable-for-caenorhabditis-elegans-development-but-suppresses-rna-dna-hybrid-associated-repeat-instability
#11
Peter Zeller, Jan Padeken, Robin van Schendel, Veronique Kalck, Marcel Tijsterman, Susan M Gasser
Histone H3 lysine 9 (H3K9) methylation is a conserved modification that generally represses transcription. In Caenorhabditis elegans it is enriched on silent tissue-specific genes and repetitive elements. In met-2 set-25 double mutants, which lack all H3K9 methylation (H3K9me), embryos differentiate normally, although mutant adults are sterile owing to extensive DNA-damage-driven apoptosis in the germ line. Transposons and simple repeats are derepressed in both germline and somatic tissues. This unprogrammed transcription correlates with increased rates of repeat-specific insertions and deletions, copy number variation, R loops and enhanced sensitivity to replication stress...
September 26, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27650246/somatically-expressed-germ-granule-components-pgl-1-and-pgl-3-repress-programmed-cell-death-in-c-elegans
#12
Mohammad Al-Amin, Hyemin Min, Yhong-Hee Shim, Ichiro Kawasaki
We previously reported that germline apoptosis in C. elegans increased by loss of PGL-1 and PGL-3, members of a family of constitutive germ-granule components, from germ cells in adult hermaphrodite gonads. In this study, we found that somatic apoptosis was reduced in synthetic multivulva class B (synMuv B) mutants due to ectopic expression of PGL-1 and PGL-3 in the soma. In synMuv B-mutant somatic cells, CED-4 expression level was reduced due to ectopic expression of PGL-1. Furthermore, in contrast to wild type, somatic apoptosis in synMuv B mutants increased following DNA damage in a SIR-2...
September 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27619188/structural-and-functional-characterisation-of-foxo-acan-daf-16-from-the-parasitic-nematode-angiostrongylus-cantonensis
#13
Baolong Yan, Weiwei Sun, Lanzhu Yan, Liangliang Zhang, Yuan Zheng, Yuzhen Zeng, Huicong Huang, Shaohui Liang
Fork head box transcription factors subfamily O (FoxO) is regarded to be significant in cell-cycle control, cell differentiation, ageing, stress response, apoptosis, tumour formation and DNA damage repair. In the free-living nematode Caenorhabditis elegans, the FoxO transcription factor is encoded by Ce-daf-16, which is negatively regulated by insulin-like signaling (IIS) and involved in promoting dauer formation through bringing about its hundreds of downstream genes expression. In nematode parasites, orthologues of daf-16 from several species have been identified, with functions in rescue of dauer phenotypes determined in a surrogate system C...
September 9, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27593554/null-allele-mutants-of-trt-1-the-catalytic-subunit-of-telomerase-in-caenorhabditis-elegans-are-less-sensitive-to-mn-induced-toxicity-and-daergic-degeneration
#14
Omamuyovwi M Ijomone, Mahfuzur R Miah, Tanara V Peres, Polycarp U Nwoha, Michael Aschner
Exposure to manganese (Mn) represents an environmental risk factor for Parkinson's disease (PD). Recent evidence suggests that telomerase reverse transcriptase (TERT), the catalytic subunit of mammalian telomerase participates in non-telomeric functions and may play a role in cellular protection from oxidative stress and DNA damage. trt-1 is the catalytic subunit of telomerase in Caenorhabditis elegans (C. elegans). The present study investigated the relationship between trt-1 mutation and Mn-induced neurotoxicity...
September 1, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27582048/fudr-extends-the-lifespan-of-the-short-lived-ap-endonuclease-mutant-in-caenorhabditis-elegans-in-a-fertility-dependent-manner
#15
Yuichi Kato, Masahiro Miyaji, Qiu-Mei Zhang-Akiyama
The anticancer drug 5-fluorouracil (5-FU) and its metabolite 5-fluoro-2'-deoxyuridine (FUdR) inhibit thymidylate synthase and induce uracil bases in DNA. FUdR is commonly used for inhibiting fertility when measuring the lifespan of the nematode Caenorhabditis elegans. However, it is not known whether DNA damage induced by FUdR affects lifespan. EXO-3 is an apurinic/apyrimidinic endonuclease in C. elegans, and we reported previously that deletion of the exo-3 gene causes reproductive abnormalities and decreased lifespan...
August 31, 2016: Genes & Genetic Systems
https://www.readbyqxmd.com/read/27561390/the-tumour-suppressor-cyld-regulates-the-p53-dna-damage-response
#16
Vanesa Fernández-Majada, Patrick-Simon Welz, Maria A Ermolaeva, Michael Schell, Alexander Adam, Felix Dietlein, David Komander, Reinhard Büttner, Roman K Thomas, Björn Schumacher, Manolis Pasparakis
The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and skin tumorigenesis. Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress...
August 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27551500/%C3%AE-tat1-downregulation-induces-mitotic-catastrophe-in-hela-and-a549-cells
#17
J-Y Chien, S-D Tsen, C-C Chien, H-W Liu, C-Y Tung, C-H Lin
α-Tubulin acetyltransferase 1 (αTAT1) controls reversible acetylation on Lys40 of α-tubulin and modulates multiple cellular functions. αTAT1 depletion induced morphological defects of touch receptor neurons in Caenorhabditis elegans and impaired cell adhesion and contact inhibition in mouse embryonic fibroblasts, however, no morphological or proliferation defects in human RPE-hTERT cells were found after αTAT1-specific siRNA treatment. Here, we compared the effect of three αTAT1-specific shRNAs on proliferation and morphology in two human cell lines, HeLa and A549...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27550812/non-transcriptional-function-of-foxo1-daf-16-contributes-to-translesion-dna-synthesis
#18
Hiroaki Daitoku, Yuta Kaneko, Kenji Yoshimochi, Kaori Matsumoto, Sho Araoi, Jun-Ichi Sakamaki, Yuta Takahashi, Akiyoshi Fukamizu
Forkhead box O (FOXO; DAF-16 in nematode) transcription factors activate a program of genes that control stress resistance, metabolism, and lifespan. Given the adverse impact of the stochastic DNA damage on organismal development and ageing, we examined the role of FOXO/DAF-16 in UV-induced DNA-damage response. Knockdown of FOXO1, but not FOXO3a, increases sensitivity to UV irradiation when exposed during S phase, suggesting a contribution of FOXO1 to translesion DNA synthesis (TLS), a replicative bypass of UV-induced DNA lesions...
August 22, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27389785/the-application-of-the-comet-assay-to-assess-the-genotoxicity-of-environmental-pollutants-in-the-nematode-caenorhabditis-elegans
#19
Soudabeh Imanikia, Francesca Galea, Eszter Nagy, David H Phillips, Stephen R Stürzenbaum, Volker M Arlt
This study aimed to establish a protocol for cell dissociation from the nematode Caenorhabditis elegans (C. elegans) to assess the genotoxicity of the environmental pollutant benzo[a]pyrene (BaP) using the alkaline version of the single cell electrophoresis assay (comet assay). BaP genotoxicity was assessed in C. elegans (wild-type [WT]; N2, Bristol) after 48h exposure (0-40μM). Induction of comets by BaP was concentration-dependent up to 20μM; comet% tail DNA was ∼30% at 20μM BaP and ∼10% in controls...
July 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27341616/identification-of-conserved-mel-28-elys-domains-with-essential-roles-in-nuclear-assembly-and-chromosome-segregation
#20
Georgina Gómez-Saldivar, Anita Fernandez, Yasuhiro Hirano, Michael Mauro, Allison Lai, Cristina Ayuso, Tokuko Haraguchi, Yasushi Hiraoka, Fabio Piano, Peter Askjaer
Nucleoporins are the constituents of nuclear pore complexes (NPCs) and are essential regulators of nucleocytoplasmic transport, gene expression and genome stability. The nucleoporin MEL-28/ELYS plays a critical role in post-mitotic NPC reassembly through recruitment of the NUP107-160 subcomplex, and is required for correct segregation of mitotic chromosomes. Here we present a systematic functional and structural analysis of MEL-28 in C. elegans early development and human ELYS in cultured cells. We have identified functional domains responsible for nuclear envelope and kinetochore localization, chromatin binding, mitotic spindle matrix association and chromosome segregation...
June 2016: PLoS Genetics
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