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https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#1
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538144/probing-the-potential-role-of-non-b-dna-structures-at-yeast-meiosis-specific-dna-double-strand-breaks
#2
Rucha Kshirsagar, Krishnendu Khan, Mamata V Joshi, Ramakrishna V Hosur, K Muniyappa
A plethora of evidence suggests that different types of DNA quadruplexes are widely present in the genome of all organisms. The existence of a growing number of proteins that selectively bind and/or process these structures underscores their biological relevance. Moreover, G-quadruplex DNA has been implicated in the alignment of four sister chromatids by forming parallel guanine quadruplexes during meiosis; however, the underlying mechanism is not well defined. Here we show that a G/C-rich motif associated with a meiosis-specific DNA double-strand break (DSB) in Saccharomyces cerevisiae folds into G-quadruplex, and the C-rich sequence complementary to the G-rich sequence forms an i-motif...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28537809/association-of-three-single-nucleotide-polymorphisms-in-mtr-and-mtrr-genes-with-lung-cancer-in-a-turkish-population
#3
Pinar Aksoy-Sagirli, Ayçin Erdenay, Esra Kaytan-Saglam, Ahmet Kizir
AIMS: Folate metabolism plays a critical role in DNA methylation and synthesis. Polymorphisms in folate metabolism may affect enzyme activities and thereby affect the cancer risk. Methionine synthase (MTR) and methionine synthase reductase (MTRR) are critical enzymes for the folate cycle. In this study, possible associations between genetic variabilities in MTR and MTRR and susceptibility to lung cancer (LC) were investigated in a Turkish population. METHODS: A case-control study with 193 LC cases and 199 noncancerous controls was conducted...
May 24, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28537806/analytic-and-clinical-validation-of-an-ultrasensitive-quantitative-polymerase-chain-reaction-assay-for-egfr-mutation-analysis-with-circulating-tumor-dna
#4
Xiaowei Wang, Yunhua Gao, Bei Wang, Zhenrong Zhang, Chaoyang Liang, Hongxiang Feng, Yongqing Guo, Jiping Da, Minli Mo, Mengyun Zhang, Feng Ding, Zhao Chen, Hui Li, Deruo Liu
CONTEXT: - The mutation analysis of epidermal growth factor receptor (EGFR) has become a common test to guide therapeutic decision making for lung cancer. Molecular testing with circulating tumor DNA in plasma allows diagnosis of mutations when tumor tissue is not available as well as monitoring treatment response with repeat biopsies. OBJECTIVES: - To develop a timely and cost-effective assay that can accurately detect EGFR mutations in circulating tumor DNA and to evaluate the analytic and clinical performance of the assay...
May 24, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28535641/-effect-of-interleukin-6-promoter-dna-methylation-on-the-pathogenesis-of-systemic-lupus-erythematosus
#5
X Y Cai, Y Lu, C Tang, X J Lin, J H Ye, W N Li, Z X He, F F Li
Objective: To analyze peripheral blood interleukin-6 (IL-6) promoter DNA methylation status and its clinical significance in patients with systemic lupus erythematosus (SLE). Methods: Blood samples of 41 adult patients with SLE and 20 healthy controls were collected.The methylation status of IL-6 promoter was determined by methylation specific polymerase chain reaction (MSP). The IL-6 expression was detected by real-time PCR.Correlations between IL-6 promoter methylation status and clinical features or laboratory findings in patients with SLE were analyzed...
May 23, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28535142/srs2-promotes-synthesis-dependent-strand-annealing-by-disrupting-dna-polymerase-%C3%AE-extending-d-loops
#6
Jie Liu, Christopher Ede, William D Wright, Steven K Gore, Shirin S Jenkins, Bret D Freudenthal, M Todd Washington, Xavier Veaute, Wolf-Dietrich Heyer
Synthesis-dependent strand annealing (SDSA) is the preferred mode of homologous recombination in somatic cells leading to an obligatory non-crossover outcome, thus avoiding the potential for chromosomal rearrangements and loss of heterozygosity. Genetic analysis identified the Srs2 helicase as a prime candidate to promote SDSA. Here, we demonstrate that Srs2 disrupts D-loops in an ATP-dependent fashion and with a distinct polarity. Specifically, we partly reconstitute the SDSA pathway using Rad51, Rad54, RPA, RFC, DNA Polymerase δ with different forms of PCNA...
May 23, 2017: ELife
https://www.readbyqxmd.com/read/28534829/variation-in-the-genetic-repertoire-of-viruses-infecting-micromonas-pusilla-reflects-horizontal-gene-transfer-and-links-to-their-environmental-distribution
#7
Jan F Finke, Danielle M Winget, Amy M Chan, Curtis A Suttle
Prasinophytes, a group of eukaryotic phytoplankton, has a global distribution and is infected by large double-stranded DNA viruses (prasinoviruses) in the family Phycodnaviridae. This study examines the genetic repertoire, phylogeny, and environmental distribution of phycodnaviruses infecting Micromonas pusilla, other prasinophytes and chlorophytes. Based on comparisons among the genomes of viruses infecting M. pusilla and other phycodnaviruses, as well as the genome from a host isolate of M. pusilla, viruses infecting M...
May 19, 2017: Viruses
https://www.readbyqxmd.com/read/28534707/type-ia-topoisomerases-can-be-magicians-for-both-dna-and-rna-in-all-domains-of-life
#8
Muzammil Ahmad, Dongyi Xu, Weidong Wang
Topoisomerases solve critical topological problems in DNA metabolism and have long been regarded as the "magicians" of the DNA world. Here we present views from two of our recent studies indicating that Type IA topoisomerases from all domains of life often possess dual topoisomerase activities for both DNA and RNA. In animals, one of the two Type IA topoisomerases, Top3β, contains an RNA-binding domain, possesses RNA topoisomerase activity, binds mRNAs, interacts with mRNA-binding proteins, and associates with active mRNA translation machinery...
May 23, 2017: RNA Biology
https://www.readbyqxmd.com/read/28534480/molecular-basis-for-primpol-recruitment-to-replication-forks-by-rpa
#9
Thomas A Guilliam, Nigel C Brissett, Aaron Ehlinger, Benjamin A Keen, Peter Kolesar, Elaine M Taylor, Laura J Bailey, Howard D Lindsay, Walter J Chazin, Aidan J Doherty
DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in the presence of such impediments. In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multifunctional replicative enzyme called primase-polymerase (PrimPol) that is capable of directly bypassing DNA damage by TLS, as well as repriming replication downstream of impediments. Here, we report that PrimPol is recruited to reprime through its interaction with RPA...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28533985/metabarcoding-monitoring-analysis-the-pros-and-cons-of-using-co-extracted-environmental-dna-and-rna-data-to-assess-offshore-oil-production-impacts-on-benthic-communities
#10
Olivier Laroche, Susanna A Wood, Louis A Tremblay, Gavin Lear, Joanne I Ellis, Xavier Pochon
Sequencing environmental DNA (eDNA) is increasingly being used as an alternative to traditional morphological-based identification to characterize biological assemblages and monitor anthropogenic impacts in marine environments. Most studies only assess eDNA which, compared to eRNA, can persist longer in the environment after cell death. Therefore, eRNA may provide a more immediate census of the environment due to its relatively weaker stability, leading some researchers to advocate for the use of eRNA as an additional, or perhaps superior proxy for portraying ecological changes...
2017: PeerJ
https://www.readbyqxmd.com/read/28533123/molecular-characterization-of-caulobacter-crescentus-mutator-strains
#11
Marinalva Martins-Pinheiro, Alice R Oliveira, Alexy O Valencia, Frank S Fernandez-Silva, Larissa G Silva, Carina O Lopes-Kulishev, Valeria C S Italiani, Marilis V Marques, Carlos F Menck, Rodrigo S Galhardo
Mutator strains were identified by screening random Tn5 insertion clones of Caulobacter crescentus. We identified clones with robust increases in mutation rates with Tn5 insertions in the mutY, mutS, mutL and uvrD genes, known to act in mutation-preventing pathways in Escherichia coli. Analysis of mutations in the rpoB gene revealed that in both the parental strain and mismatch repair-deficient mutants, A:T→G:C transitions predominate by a large margin over C:G→T:A. We have also investigated the role of the error-prone polymerase encoded by imuC (dnaE2) in spontaneous mutagenesis, and found that a imuC mutant strain shows mutation rates and sequences comparable to the parental strain...
May 19, 2017: Gene
https://www.readbyqxmd.com/read/28532341/pterostilbene-protects-against-uvb-induced-photo-damage-through-a-phosphatidylinositol-3-kinase-dependent-nrf2-are-pathway-in-human-keratinocytes
#12
Huaping Li, Na Jiang, Bihua Liang, Qing Liu, Erting Zhang, Liqian Peng, Huiyan Deng, Runxiang Li, Zhenjie Li, Huilan Zhu
OBJECTIVE: Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes. METHODS: Human keratinocytes were pretreated with Pter (5 and 10 μM) for 24 h prior to UVB irradiation (300 mJ/cm(2))...
May 22, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28531958/unique-postglacial-evolution-of-the-hornbeam-carpinus-betulus-l-in-the-carpathians-and-the-balkan-peninsula-revealed-by-chloroplast-dna
#13
Dragoş Postolache, Flaviu Popescu, Ladislav Paule, Dalibor Ballian, Peter Zhelev, Sorina Fărcaş, Juraj Paule, Ovidiu Badea
The Balkan Peninsula is one of the largest and most important European glacial refugia. However, the evolutionary history and phylogeographic pattern of temperate tree species that survived in the Balkans glacial refugia and their contribution to the genetic structure of the current population in the Carpathian Mountains remains poorly understood. Using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), and extensive population sampling, we explored the phylogeographic pattern of Carpinus betulus in both the Balkan Peninsula and the Carpathian region...
May 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28531327/interstrand-cross-links-arising-from-strand-breaks-at-true-abasic-sites-in-duplex-dna
#14
Zhiyu Yang, Nathan E Price, Kevin M Johnson, Yinsheng Wang, Kent S Gates
Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. Abasic (Ap) sites are common lesions in genomic DNA that readily undergo spontaneous and amine-catalyzed strand cleavage reactions that generate a 2,3-didehydro-2,3-dideoxyribose sugar remnant (3'ddR5p) at the 3'-terminus of the strand break. Interestingly, this strand scission process leaves an electrophilic α,β-unsaturated aldehyde residue embedded within the resulting nicked duplex...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531315/the-interaction-between-cytosine-methylation-and-processes-of-dna-replication-and-repair-shape-the-mutational-landscape-of-cancer-genomes
#15
Rebecca C Poulos, Jake Olivier, Jason W H Wong
Methylated cytosines (5mCs) are frequently mutated in the genome. However, no studies have yet comprehensively analysed mutation-methylation associations across cancer types. Here we analyse 916 cancer genomes, together with tissue type-specific methylation and replication timing data. We describe a strong mutation-methylation association across colorectal cancer subtypes, most interestingly in samples with microsatellite instability (MSI) or Polymerase epsilon (POLE) exonuclease domain mutations. By analysing genomic regions with differential mismatch repair (MMR) efficiency, we suggest a possible role for MMR in the correction of 5mC deamination events, potentially accounting for the high rate of 5mC mutation accumulation in MSI tumours...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531304/replication-studies-of-carboxymethylated-dna-lesions-in-human-cells
#16
Jun Wu, Pengcheng Wang, Lin Li, Nicole L Williams, Debin Ji, Walter J Zahurancik, Changjun You, Jianshuang Wang, Zucai Suo, Yinsheng Wang
Metabolic activation of some N-nitroso compounds (NOCs), an important class of DNA damaging agents, can induce the carboxymethylation of nucleobases in DNA. Very little was previously known about how the carboxymethylated DNA lesions perturb DNA replication in human cells. Here, we investigated the effects of five carboxymethylated DNA lesions, i.e. O6-CMdG, N6-CMdA, N4-CMdC, N3-CMdT and O4-CMdT on the efficiency and fidelity of DNA replication in HEK293T human embryonic kidney cells. We found that, while neither N6-CMdA nor N4-CMdC blocked DNA replication or induced mutations, N3-CMdT, O4-CMdT and O6-CMdG moderately blocked DNA replication and induced substantial frequencies of T→A (81%), T→C (68%) and G→A (6...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531167/a-role-for-the-host-dna-damage-response-in-hepatitis-b-virus-cccdna-formation-and-beyond
#17
REVIEW
Sabrina Schreiner, Michael Nassal
Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is converted into nuclear covalently closed circular (ccc) DNA. Associating with cellular proteins into an episomal minichromosome, cccDNA acts as template for new viral RNAs, ensuring formation of progeny virions...
May 22, 2017: Viruses
https://www.readbyqxmd.com/read/28529628/cross-platform-comparison-of-four-leading-technologies-for-detecting-egfr-mutations-in-circulating-tumor-dna-from-non-small-cell-lung-carcinoma-patient-plasma
#18
Ting Xu, Xiaozheng Kang, Xiaofang You, Liang Dai, Dequan Tian, Wanpu Yan, Yongbo Yang, Hongchao Xiong, Zhen Liang, Grace Q Zhao, Shengrong Lin, Ke-Neng Chen, Guobing Xu
Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), especially when representative tissue biopsies are not available. Here, we have compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients. Two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction (ddPCR) and a next-generation sequencing (Firefly NGS) platform were included in the comparison...
2017: Theranostics
https://www.readbyqxmd.com/read/28529617/combined-detection-of-plasma-zic1-hoxd10-and-runx3-methylation-is-a-promising-strategy-for-early-detection-of-gastric-cancer-and-precancerous-lesions
#19
Zhenghua Lin, Mengzhao Luo, Xueqing Chen, Xingkang He, Yun Qian, Sanchuan Lai, Jianmin Si, Shujie Chen
We try to explore the value of aberrant DNA methylation of several cancer-related genes in plasma as non-invasive biomarkers for gastric cancer (GC) and precancerous lesions. By using methylation-specific polymerase chain reaction assay we determined the methylation status of three selected genes ZIC1, HOXD10 and RUNX3 in blood samples from patients with GC and precancerous lesions. We discovered that the methylation rate of ZIC1, HOXD10 and RUNX3 increased significantly in the progression of gastric carcinogenesis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28529609/is-pretreatment-epstein-barr-virus-dna-still-associated-with-6-year-survival-outcomes-in-locoregionally-advanced-nasopharyngeal-carcinoma
#20
Ya-Nan Jin, Ji-Jin Yao, Fan Zhang, Si-Yang Wang, Wang-Jian Zhang, Guan-Qun Zhou, Zhen-Yu Qi, Ying Sun
Purpose: The objective of this study was to confirm the association between pretreatment Epstein-Barr virus (EBV) DNA (pre-DNA) load and survival outcomes after long-term follow-up in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Materials and Methods: Between November 2009 and February 2012, a total of 1036 patients with LA-NPC were enrolled. There were 762 patients in stage III and 274 in stage IVA-B. All patients were treated with radical radiotherapy with or without chemotherapy, and pre-DNA concentrations were quantified by a polymerase chain reaction assay...
2017: Journal of Cancer
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