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https://www.readbyqxmd.com/read/28934497/systematic-analysis-of-dna-crosslink-repair-pathways-during-development-and-aging-in-caenorhabditis-elegans
#1
David M Wilson, Matthias Rieckher, Ashley B Williams, Björn Schumacher
DNA interstrand crosslinks (ICLs) are generated by endogenous sources and chemotherapeutics, and pose a threat to genome stability and cell survival. Using Caenorhabditis elegans mutants, we identify DNA repair factors that protect against the genotoxicity of ICLs generated by trioxsalen/ultraviolet A (TMP/UVA) during development and aging. Mutations in nucleotide excision repair (NER) components (e.g. XPA-1 and XPF-1) imparted extreme sensitivity to TMP/UVA relative to wild-type animals, manifested as developmental arrest, defects in adult tissue morphology and functionality, and shortened lifespan...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934494/derivatives-of-bst-like-gss-polymerase-with-improved-processivity-and-inhibitor-tolerance
#2
Igor P Oscorbin, Ekaterina A Belousova, Ulyana A Boyarskikh, Aleksandr I Zakabunin, Evgeny A Khrapov, Maksim L Filipenko
At the moment, one of the actual trends in medical diagnostics is a development of methods for practical applications such as point-of-care testing, POCT or research tools, for example, whole genome amplification, WGA. All the techniques are based on using of specific DNA polymerases having strand displacement activity, high synthetic processivity, fidelity and, most significantly, tolerance to contaminants, appearing from analysed biological samples or collected under purification procedures. Here, we have designed a set of fusion enzymes based on catalytic domain of DNA polymerase I from Geobacillus sp...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934488/de-novo-pathway-based-biomarker-identification
#3
Nicolas Alcaraz, Markus List, Richa Batra, Fabio Vandin, Henrik J Ditzel, Jan Baumbach
Gene expression profiles have been extensively discussed as an aid to guide the therapy by predicting disease outcome for the patients suffering from complex diseases, such as cancer. However, prediction models built upon single-gene (SG) features show poor stability and performance on independent datasets. Attempts to mitigate these drawbacks have led to the development of network-based approaches that integrate pathway information to produce meta-gene (MG) features. Also, MG approaches have only dealt with the two-class problem of good versus poor outcome prediction...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934474/human-dna-polymerase-delta-double-mutant-d316a-e318a-interferes-with-dna-mismatch-repair-in-vitro
#4
Dekang Liu, Jane H Frederiksen, Sascha E Liberti, Anne Lützen, Guido Keijzers, Javier Pena-Diaz, Lene Juel Rasmussen
DNA mismatch repair (MMR) is a highly-conserved DNA repair mechanism, whose primary role is to remove DNA replication errors preventing them from manifesting as mutations, thereby increasing the overall genome stability. Defects in MMR are associated with increased cancer risk in humans and other organisms. Here, we characterize the interaction between MMR and a proofreading-deficient allele of the human replicative DNA polymerase delta, PolδD316A;E318A, which has a higher capacity for strand displacement DNA synthesis than wild type Polδ...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28933854/epigenetic-dna-modification-n6-methyladenine-causes-site-specific-rna-polymerase-ii-transcriptional-pausing
#5
Wei Wang, Liang Xu, Lulu Hu, Jenny Chong, Chuan He, Dong Wang
N6-methyladenine (N6-mA or 6mA) is an epigenetic DNA modification in eukaryotic genomes. In contrast to the well-established roles of 5-methylcytosine for epigenetic regulation of gene expression, the functional roles of N6-mA remain elusive. In particular, the impact of N6-mA modification at DNA template on RNA polymerase II (pol II) transcription elongation is not known. In this work, using the Saccharomyces cerevisiae pol II transcriptional elongation system as a model, we investigated the molecular mechanism of pol II recognition and processing of N6-mA sites via both biochemical and structural approaches...
September 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28933543/prevalent-sequences-in-the-human-genome-can-form-mini-i-motif-structures-at-physiological-ph
#6
Bartomeu Mir, Israel Serrano, Diana Buitrago, Modesto Orozco, Nuria Escaja, Carlos González
We report here the solution structure of several repetitive DNA sequences containing d(TCGTTCCGT) and related repeats. At physiological pH, these sequences fold into an i-motif like quadruplexes in which every two repeats a globular structure is stabilized by two hemiprotonated C:C+ base pairs, flanked by two minor groove tetrads resulting from the association of G:C or G:T base pairs. The interaction between the minor groove tetrads and the nearby C:C+ base pairs affords a strong stabilization, which results in effective pHT values above 7...
September 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28932904/a-computational-method-using-the-random-walk-with-restart-algorithm-for-identifying-novel-epigenetic-factors
#7
JiaRui Li, Lei Chen, ShaoPeng Wang, YuHang Zhang, XiangYin Kong, Tao Huang, Yu-Dong Cai
Epigenetic regulation has long been recognized as a significant factor in various biological processes, such as development, transcriptional regulation, spermatogenesis, and chromosome stabilization. Epigenetic alterations lead to many human diseases, including cancer, depression, autism, and immune system defects. Although efforts have been made to identify epigenetic regulators, it remains a challenge to systematically uncover all the components of the epigenetic regulation in the genome level using experimental approaches...
September 20, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28932682/stroke-associated-pattern-of-gene-expression-previously-identified-by-machine-learning-is-diagnostically-robust-in-an-independent-patient-population
#8
Grant C O'Connell, Paul D Chantler, Taura L Barr
Our group recently employed genome-wide transcriptional profiling in tandem with machine-learning based analysis to identify a ten-gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population. Publicly available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 h post-symptom onset, as well from 23 cardiovascular disease controls, were obtained via the National Center for Biotechnology Information Gene Expression Omnibus...
December 2017: Genomics Data
https://www.readbyqxmd.com/read/28928764/exploring-and-harnessing-haplotype-diversity-to-improve-yield-stability-in-crops
#9
REVIEW
Lunwen Qian, Lee T Hickey, Andreas Stahl, Christian R Werner, Ben Hayes, Rod J Snowdon, Kai P Voss-Fels
In order to meet future food, feed, fiber, and bioenergy demands, global yields of all major crops need to be increased significantly. At the same time, the increasing frequency of extreme weather events such as heat and drought necessitates improvements in the environmental resilience of modern crop cultivars. Achieving sustainably increase yields implies rapid improvement of quantitative traits with a very complex genetic architecture and strong environmental interaction. Latest advances in genome analysis technologies today provide molecular information at an ultrahigh resolution, revolutionizing crop genomic research, and paving the way for advanced quantitative genetic approaches...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28928377/viral-outbreaks-involve-destabilized-evolutionary-networks-evidence-from-ebola-influenza-and-zika
#10
Stéphane Aris-Brosou, Neke Ibeh, Jessica Noël
Recent history has provided us with one pandemic (Influenza A/H1N1) and two severe viral outbreaks (Ebola and Zika). In all three cases, post-hoc analyses have given us deep insights into what triggered these outbreaks, their timing, evolutionary dynamics, and phylogeography, but the genomic characteristics of outbreak viruses are still unclear. To address this outstanding question, we searched for a common denominator between these recent outbreaks, positing that the genome of outbreak viruses is in an unstable evolutionary state, while that of non-outbreak viruses is stabilized by a network of correlated substitutions...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928239/the-rna-editing-enzyme-adar-promotes-lung-adenocarcinoma-migration-and-invasion-by-stabilizing-fak
#11
Elianna M Amin, Yuan Liu, Su Deng, Kay See Tan, Neel Chudgar, Marty W Mayo, Francisco Sanchez-Vega, Prasad S Adusumilli, Nikolaus Schultz, David R Jones
Large-scale, genome-wide studies report that RNA binding proteins are altered in cancers, but it is unclear how these proteins control tumor progression. We found that the RNA-editing protein ADAR (adenosine deaminase acting on double-stranded RNA) acted as a facilitator of lung adenocarcinoma (LUAD) progression through its ability to stabilize transcripts encoding focal adhesion kinase (FAK). In samples from 802 stage I LUAD patients, increased abundance of ADAR at both the mRNA and protein level correlated with tumor recurrence...
September 19, 2017: Science Signaling
https://www.readbyqxmd.com/read/28927527/dna-mismatch-repair-and-its-many-roles-in-eukaryotic-cells
#12
REVIEW
Dekang Liu, Guido Keijzers, Lene Juel Rasmussen
DNA mismatch repair (MMR) is an important DNA repair pathway that plays critical roles in DNA replication fidelity, mutation avoidance and genome stability, all of which contribute significantly to the viability of cells and organisms. MMR is widely-used as a diagnostic biomarker for human cancers in the clinic, and as a biomarker of cancer susceptibility in animal model systems. Prokaryotic MMR is well-characterized at the molecular and mechanistic level; however, MMR is considerably more complex in eukaryotic cells than in prokaryotic cells, and in recent years, it has become evident that MMR plays novel roles in eukaryotic cells, several of which are not yet well-defined or understood...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28926746/effect-of-modeled-microgravity-on-uv-c-induced-interplant-communication-of-arabidopsis-thaliana
#13
Ting Wang, Wei Xu, Huasheng Li, Chenguang Deng, Hui Zhao, Yuejin Wu, Min Liu, Lijun Wu, Jinying Lu, Po Bian
Controlled ecological life support systems (CELSS) will be an important feature of long-duration space missions of which higher plants are one of the indispensable components. Because of its pivotal role in enabling plants to cope with environmental stress, interplant communication might have important implications for the ecological stability of such CELSS. However, the manifestations of interplant communication in microgravity conditions have yet to be fully elucidated. To address this, a well-established Arabidopsis thaliana co-culture experimental system, in which UV-C-induced airborne interplant communication is evaluated by the alleviation of transcriptional gene silencing (TGS) in bystander plants, was placed in microgravity modeled by a two-dimensional rotating clinostat...
September 6, 2017: Mutation Research
https://www.readbyqxmd.com/read/28925409/metabolic-and-genomic-adaptations-to-winter-fattening-in-a-primate-species-the-grey-mouse-lemur-microcebus-murinus
#14
J Terrien, M Gaudubois, D Champeval, V Zaninotto, L Roger, J F Riou, F Aujard
AIM: To understand the mechanisms underlying the development of metabolic changes leading to obesity remains a major world health issue. Among such mechanisms, seasonality is quite underestimated although it corresponds to the manifestation of extreme metabolic flexibility in response to a changing environment. Nevertheless, the changes induced by such flexibility are far to be understood, especially at the level of insulin signaling, genomic stability or inflammation. METHODS: Here, we investigated the metabolic regulations displayed by a seasonal primate species, the grey mouse lemur (Microcebus murinus) that exhibits pronounced changes in body mass during the 6-month winter season: a fattening period followed by a spontaneous fat loss, without ever reaching pathological stages...
August 14, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28925386/5-hydroxymethylcytosine-signatures-in-circulating-cell-free-dna-as-diagnostic-biomarkers-for-human-cancers
#15
Wenshuai Li, Xu Zhang, Xingyu Lu, Lei You, Yanqun Song, Zhongguang Luo, Jun Zhang, Ji Nie, Wanwei Zheng, Diannan Xu, Yaping Wang, Yuanqiang Dong, Shulin Yu, Jun Hong, Jianping Shi, Hankun Hao, Fen Luo, Luchun Hua, Peng Wang, Xiaoping Qian, Fang Yuan, Lianhuan Wei, Ming Cui, Taiping Zhang, Quan Liao, Menghua Dai, Ziwen Liu, Ge Chen, Katherine Meckel, Sarbani Adhikari, Guifang Jia, Marc B Bissonnette, Xinxiang Zhang, Yupei Zhao, Wei Zhang, Chuan He, Jie Liu
DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals...
September 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28924389/structural-maintenance-of-chromosomes-protein-1-role-in-genome-stability-and-tumorigenesis
#16
REVIEW
Fei Yi, Zhuo Wang, Jingwei Liu, Ying Zhang, Zhijun Wang, Hongde Xu, Xiaoman Li, Ning Bai, Liu Cao, Xiaoyu Song
SMC1 (Structural Maintenance of Chromosomes protein 1), well known as one of the SMC superfamily members, has been explored to function in many activities including chromosome dynamics, cell cycle checkpoint, DNA damage repair and genome stability. Upon being properly assembled as part of cohesin, SMC1 can be phosphorylated by ATM and mediate downstream DNA damage repair after ionizing irradiation. Abnormal gene expression or mutation of SMC1 can cause defect in the DNA damage repair pathway, which has been strongly associated with tumorigenesis...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28924219/mesoscopic-model-for-dna-g-quadruplex-unfolding
#17
A E Bergues-Pupo, I Gutiérrez, J R Arias-Gonzalez, F Falo, A Fiasconaro
Genomes contain rare guanine-rich sequences capable of assembling into four-stranded helical structures, termed G-quadruplexes, with potential roles in gene regulation and chromosome stability. Their mechanical unfolding has only been reported to date by all-atom simulations, which cannot dissect the major physical interactions responsible for their cohesion. Here, we propose a mesoscopic model to describe both the mechanical and thermal stability of DNA G-quadruplexes, where each nucleotide of the structure, as well as each central cation located at the inner channel, is mapped onto a single bead...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924058/localization-of-cdc7-protein-kinase-during-dna-replication-in-saccharomyces-cerevisiae
#18
Daniel Rossbach, D Suzi Bryan, Jay R Hesselberth, Robert Sclafani
DDK, a conserved serine-threonine protein kinase composed of a regulatory subunit, Dbf4, and a catalytic subunit, Cdc7, is essential for DNA replication initiation during S phase of the cell cycle through MCM2-7 helicase phosphorylation. The biological significance of DDK is well characterized, but the full mechanism of how DDK associates with substrates remains unclear. Cdc7 is bound to chromatin in the Saccharomyces cerevisiae genome throughout the cell cycle, but there is little empirical evidence as to specific Cdc7 binding locations...
September 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28923882/mutational-profiling-of-acute-myeloid-leukemia-with-normal-cytogenetics-in-brazilian-patients-the-value-of-next-generation-sequencing-for-genomic-classification
#19
Thiago Rodrigo de Noronha, Miguel Mitne-Neto, Maria de Lourdes Chauffaille
Karyotype (KT) aberrations are important prognostic factors for acute myeloid leukemia (AML); however, around 50% of cases present normal results. Single nucleotide polymorphism array can detect chromosomal gains, losses or uniparental disomy that are invisible to KT, thus improving patients' risk assessment. However, when both tests are normal, important driver mutations can be detected by the use of next-generation sequencing (NGS). Fourteen adult patients with AML with normal cytogenetics were investigated by NGS for 19 AML-related genes...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28922599/effect-of-t%C3%A2-t-mismatch-on-dna-dynamics-probed-by-minor-groove-binders-comparison-of-dynamic-stokes-shifts-of-hoechst-and-dapi
#20
Him Shweta, Moirangthem Kiran Singh, Kavita Yadav, Sachin Dev Verma, Nibedita Pal, Sobhan Sen
Recognition of DNA base mismatches and their subsequent repair by enzymes is vital for genomic stability. However, it is difficult to comprehend such process in which enzymes sense and repair different types of mismatches with different ability. It has been suggested that the differential structural changes of mismatched-bases act as cues to the repair enzymes, although effect of such DNA structural changes on surrounding water and ion dynamics is inevitable due to strong electrostatic coupling among them. Thus, collective dynamics of DNA, water and ions near the mismatch site is believed to be important for mismatch recognition and repair mechanism...
September 18, 2017: Journal of Physical Chemistry. B
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