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Non canonical DNA

Sandra Käppel, Rainer Melzer, Florian Rümpler, Christian Gafert, Günter Theißen
SEPALLATA3 of Arabidopsis thaliana is a MADS-domain transcription factor and a key regulator of flower development. MADS-domain proteins bind to sequences termed 'CArG-boxes' (consensus 5'-CC(A/T)6 GG-3'). Since only a fraction of the CArG-boxes in the Arabidopsis genome are bound by SEPALLATA3, more elaborate principles have to be discovered to better understand which features turn CArG-boxes into genuine recognition sites. Here, we investigate to which extent the shape of the DNA is involved in a 'shape readout' that contributes to the binding of SEPALLATA3...
May 9, 2018: Plant Journal: for Cell and Molecular Biology
Laura Nicolas, Montserrat Cols, Jee Eun Choi, Jayanta Chaudhuri, Bao Vuong
Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR...
2018: F1000Research
Pengxu Qian, Bony De Kumar, Xi C He, Christof Nolte, Madelaine Gogol, Youngwook Ahn, Shiyuan Chen, Zhenrui Li, Hanzhang Xu, John M Perry, Deqing Hu, Fang Tao, Meng Zhao, Yingli Han, Kate Hall, Allison Peak, Ariel Paulson, Chongbei Zhao, Aparna Venkatraman, Andrew Box, Anoja Perera, Jeffrey S Haug, Tari Parmely, Hua Li, Robb Krumlauf, Linheng Li
Hox genes modulate the properties of hematopoietic stem cells (HSCs) and reacquired Hox expression in progenitors contributes to leukemogenesis. Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling genes are predominantly enriched in LT-HSCs, and this coordinate regulation of Hoxb expression is mediated by a retinoid-dependent cis-regulatory element, distal element RARE (DERARE). Deletion of the DERARE reduced Hoxb expression, resulting in changes to many downstream signaling pathways (e...
May 3, 2018: Cell Stem Cell
Jingyi Wu, Jiawei Xu, Bofeng Liu, Guidong Yao, Peizhe Wang, Zili Lin, Bo Huang, Xuepeng Wang, Tong Li, Senlin Shi, Nan Zhang, Fuyu Duan, Jia Ming, Xiangyang Zhang, Wenbin Niu, Wenyan Song, Haixia Jin, Yihong Guo, Shanjun Dai, Linli Hu, Lanlan Fang, Qiujun Wang, Yuanyuan Li, Wei Li, Jie Na, Wei Xie, Yingpu Sun
Upon fertilization, drastic chromatin reorganization occurs during preimplantation development 1 . However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored in humans. Here we investigate chromatin states in human preimplantation development using an improved assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) 2 . We find widespread accessible chromatin regions in early human embryos that overlap extensively with putative cis-regulatory sequences and transposable elements...
May 2, 2018: Nature
Aurore Guédin, Linda Yingqi Lin, Samir Armane, Laurent Lacroix, Jean-Louis Mergny, Stéphane Thore, Liliya A Yatsunyk
Guanine-rich DNA has the potential to fold into non-canonical G-quadruplex (G4) structures. Analysis of the genome of the social amoeba Dictyostelium discoideum indicates a low number of sequences with G4-forming potential (249-1055). Therefore, D. discoideum is a perfect model organism to investigate the relationship between the presence of G4s and their biological functions. As a first step in this investigation, we crystallized the dGGGGGAGGGGTACAGGGGTACAGGGG sequence from the putative promoter region of two divergent genes in D...
April 30, 2018: Nucleic Acids Research
Jacky Guy, Beatrice Alexander-Howden, Laura FitzPatrick, Dina DeSousa, Martha V Koerner, Jim Selfridge, Adrian Bird
Most missense mutations causing Rett syndrome affect domains of MeCP2 that have been shown to either bind methylated DNA or interact with a transcriptional co-repressor complex. Several mutations, however, including the C-terminal truncations that account for ∼10% of cases, fall outside these characterised domains. We studied the molecular consequences of four of these "non-canonical" mutations in cultured neurons and mice to see if they reveal additional essential domains without affecting known properties of MeCP2...
April 27, 2018: Human Molecular Genetics
M Löffler, E A Carrey, E Zameitat
Since 1956, when exogenous uridine and cytidine were found to be necessary for the maintenance of perfused rat brain function, the co-existence of de novo synthesis, salvage pathways and removal of pyrimidine bases in the CNS has been a controversial subject. Here, we review studies on metabolites and enzymes of pyrimidine metabolism through more than 60 years. In view of known and newly-described inherited pyrimidine and purine disorders - some with complex clinical profiles of neurological impairments - we underline the necessity to investigate how the different pathways work together in the developing brain and then sustain plasticity, regeneration and neuro-transmission in the adult CNS...
April 25, 2018: Nucleosides, Nucleotides & Nucleic Acids
Dieter Scharnweber, Susanne Bierbaum, Cornelia Wolf-Brandstetter
DNA sequences are widely used for gene transfer into cells including a number of substrate surface based supporting systems, but due to its singular structure property profile DNA also offers multiple options for non-canonical applications. The special case of using DNA and oligodesoxyribonucleotide (ODN) structures for surface functionalization of biomedical implants is summarized here with the major focus on (i) immobilization or anchoring of nucleic acid structures on substrate surfaces, (ii) incorporation of biologically active molecules (BAM) into such systems, and (iii) biological characteristics of the resulting surfaces in vitro and in vivo...
April 23, 2018: FEBS Letters
Rendong Yang, Jamie L Van Etten, Scott M Dehm
BACKGROUND: Insertions and deletions (indels) are a major class of genomic variation associated with human disease. Indels are primarily detected from DNA sequencing (DNA-seq) data but their transcriptional consequences remain unexplored due to challenges in discriminating medium-sized and large indels from splicing events in RNA-seq data. RESULTS: Here, we developed transIndel, a splice-aware algorithm that parses the chimeric alignments predicted by a short read aligner and reconstructs the mid-sized insertions and large deletions based on the linear alignments of split reads from DNA-seq or RNA-seq data...
April 19, 2018: BMC Genomics
Javier E Moreno, Guillermo Moreno-Piovano, Raquel L Chan
The bHLH family is composed by canonical and non-canonical transcription factors (TFs) that differ in the presence or absence of their DNA-binding domain, respectively. Since both types of bHLH proteins are able to dimerize, their relative abundance impacts their biological activity. Among this TF family BEE and IBH are canonical and non-canonical bHLHs, respectively and previous reports indicated that BEE2 and IBH1 dimerize. Wondering whether BEE TFs participate in the abiotic stress response and how the dimerization with IBH1 could regulate their role in Arabidopsis, double bee1/bee2 and triple bee1/bee2/bee3 mutants were tested under salinity and drought stresses...
June 2018: Plant Science: An International Journal of Experimental Plant Biology
Marko Trajkovski, Tamaki Endoh, Hisae Tateishi-Karimata, Tatsuya Ohyama, Shigenori Tanaka, Janez Plavec, Naoki Sugimoto
Molecular crowding conditions provided by high concentration of cosolutes are utilized for characterization of biomolecules in cell-mimicking environment and development of drug-delivery systems. In this context, (poly)ethylene glycols are often used for studying non-canonical DNA structures termed G-quadruplexes, which came into focus by emerging structural biology findings and new therapeutic drug design approaches. Recently, several reports were made arguing against using (poly)ethylene glycols in role of molecular crowding agents due to their direct impact on DNA G-quadruplex stability and topology...
April 10, 2018: Nucleic Acids Research
Peter V Deraska, Colin O'Leary, Hunter D Reavis, Shelby Labe, Tru-Khang Dinh, Jean-Bernard Lazaro, Christopher Sweeney, Alan D D'Andrea, David Kozono
Despite optimal chemotherapy, radiotherapy (RT), and/or surgery, non-small-cell lung carcinoma (NSCLC) remains the leading cause of cancer-related death in the US and worldwide. Thoracic RT, a mainstay in the treatment of locally advanced NSCLC, is often restricted in efficacy by a therapeutic index limited by sensitivity of tissues surrounding the malignancy. Therefore, radiosensitizers that can improve the therapeutic index are a vital unmet need. Inhibition of the NF-κB pathway is a proposed mechanism of radiosensitization...
December 2018: Cell Death Discovery
Xiaoxian Wu, Diane L Haakonsen, Allen G Sanderlin, Yue J Liu, Liqiang Shen, Ningning Zhuang, Michael T Laub, Yu Zhang
Canonical bacterial transcription activators bind to non-transcribed promoter elements to increase transcription of their target genes. Here we report crystal structures of binary complexes comprising domains of Caulobacter crescentus GcrA, a noncanonical bacterial transcription factor, that support a novel mechanism for transcription activation through the preferential binding of methylated cis-regulatory elements and the promotion of open complex formation through an interaction with region 2 of the principal σ factor, σ70...
April 6, 2018: Nucleic Acids Research
Micol Falabella, Rafael J Fernandez, Brad Johnson, Brett A Kaufman
Some DNA or RNA sequences rich in guanine (G) nucleotides can adopt non-canonical conformations known as G-quadruplexes (G4). In the nuclear genome, G4 motifs have been associated with genome instability and gene expression defects, but they are increasingly recognized to be regulatory structures. Recent studies have revealed that G4 structures can form in the mitochondrial genome (mtDNA) and G4 forming potential sequences are associated with the origin of mtDNA deletions. However, little is known about the regulatory role of G4 structures in mitochondria...
February 28, 2018: Current Medicinal Chemistry
Bee Gek Ng, Jae Woo Han, Dong Wan Lee, Gyung Ja Choi, Beom Seok Kim
Hahella chejuensis MB-1084 is a Gram-negative marine bacterial strain that produces unusual 17-membered carbocyclic tetraenes, chejuenolide A and B. Two fosmid clones responsible for chejuenolide production were identified from the genomic DNA library of the MB-1084 strain. Systematic inactivation of the open reading frames (ORFs) in the sequenced region defines the boundaries of the chejuenolide (che) biosynthetic gene cluster (24.9 kbp) that encodes one non-ribosomal peptide synthase (NRPS)-polyketide synthase (PKS) hybrid protein, three modular PKSs, two PKS domains, and an amine oxidase homolog...
May 2018: Journal of Antibiotics
Vladimir B Tsvetkov, Timofei S Zatsepin, Evgeny S Belyaev, Yury I Kostyukevich, George V Shpakovski, Victor V Podgorsky, Galina E Pozmogova, Anna M Varizhuk, Andrey V Aralov
Non-canonical DNA structures are widely used for regulation of gene expression, in DNA nanotechnology and for the development of new DNA-based sensors. I-motifs (iMs) are two intercalated parallel duplexes that are held together by hemiprotonated C-C base pairs. Previously, iMs were used as an accurate sensor for intracellular pH measurements. However, iM stability is moderate, which in turn limits its in vivo applications. Here, we report the rational design of a new substituted phenoxazine 2'-deoxynucleotide (i-clamp) for iM stabilization...
April 6, 2018: Nucleic Acids Research
Yossi Saragani, Amnon Hizi, Galia Rahav, Sara Zaouch, Mary Bakhanashvili
HIV-1 reverse transcriptase (RT) in the cytoplasm of HIV-infected cells efficiently inserts the non-canonical dUTP into the proviral DNA, and extends the dU-terminated DNA. The misincorporation of dUTP leads to mutagenesis, and uracils can down-regulate viral gene expression. However, uracilation might also protect HIV DNA from auto-integration in the cytoplasm. Tumor suppressor p53 protein, exhibiting inherent 3'→5' exonuclease activity, provides a potential host-derived repair mechanism during HIV reverse transcription for the misincorporation of various wrong nucleotides, leading to both base-base mismatches and incorporated non-canonical ribonucleotides...
March 4, 2018: Biochemical and Biophysical Research Communications
Laura J Eccles, Andrew C Bell, Simon N Powell
When Fanconi Anemia (FA) proteins were depleted in human U2OS cells with integrated DNA repair reporters, we observed decreases in homologous recombination (HR), decreases in mutagenic non-homologous end joining (m-NHEJ) and increases in canonical NHEJ, which was independently confirmed by measuring V(D)J recombination. Furthermore, depletion of FA proteins resulted in reduced HR protein foci and increased NHEJ protein recruitment to replication-associated DSBs, consistent with our observation that the use of canonical NHEJ increases after depletion of FA proteins in cycling cells...
April 2018: DNA Repair
Felipe Cava
In this monographic issue, we have the pleasure to present contributions from six of the leading laboratories at the forefront of Vibrio cholerae genetics, ecology and evolution, together with a brief tribute by Diego Romero to Doctor Jaime Ferrán y Clua, a pioneering Spanish bacteriologist who developed the first vaccine against this pathogen. V. cholerae is a free-living aquatic bacterium that interacts with and infects a variety of organisms. In humans it causes cholera, the deadly diarrhoea that was responsible for millions of deaths during seven pandemics since 1817, and still thousands every year...
September 2017: International Microbiology: the Official Journal of the Spanish Society for Microbiology
Daniel A Truchado, Michaël A J Moens, Sergio Callejas, Javier Pérez-Tris, Laura Benítez
Papillomaviruses are non-enveloped, DNA viruses that infect skin and mucosa of a wide variety of vertebrates, causing neoplasias or simply persisting asymptomatically. Avian papillomaviruses, with six fully sequenced genomes, are the second most studied group after mammalian papillomaviruses. In this study, we describe the first oral avian papillomavirus, detected in the tongue of a dead Yorkshire canary (Serinus canaria) and in oral swabs of the same bird and other two live canaries from an aviary in Madrid, Spain...
February 14, 2018: Veterinary Research Communications
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