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G quadruplex

Shuntaro Takahashi, Naoki Sugimoto
Nucleic acids (DNA and RNA) can form various non-canonical structures. Because some serious diseases are caused by the conformational change of G-quadruplex DNA structures, the development of ligands that bind and stabilize G-quadruplex DNA is of interest to the field of nucleic acid chemistry. Volumetric changes (ΔV) in the biomolecular reaction include the structural change of biomolecules and hydration behaviors, which provide information about the tertiary interaction between G-quadruplex DNA and ligands...
September 18, 2017: Current Protocols in Nucleic Acid Chemistry
Yang Wang, Qi Ding, Tao Xu, Chang-Yao Li, Dan-Dan Zhou, Lei Zhang
Manipulating the posttranslational modulator of p53 is central in the regulation of its activity and function. ISGylated p53 can be degraded by the 20S proteasome. During this process, HERC5/Ceb1, an IFN-induced HECT-type E3 ligase, mediated p53 ISGylation. In this study, we indicated that HERC5 was over-expressed in both HCC tissue samples and cell lines. Knockdown of HERC5 significantly induced the expression of p53, p21 and Bax/Bcl-2 in HCC cells, resulting in apoptosis augment. Whereas, opposite results were obtained by using HERC5 over-expression...
September 14, 2017: Toxicology and Applied Pharmacology
Yi Liu, Rong Liao, Huan Wang, Hang Gong, Chunyan Chen, Xiaoming Chen, Changqun Cai
A facile and cost-effective fluorescence biosensor is constructed for the accurate and sensitive determination of DNA. The G-quadruplex-forming sequence in hairpin DNA sequence (H1) is originally locked. When target DNA is present, the hairpin structure of H1 can be unfolded and part of H1 hybridized with the target DNA to form a double-stranded DNA and a G-quadruplex. The hairpin DNA sequence (H2) hybridizes with the unfolded H1 and displaces the target DNA. Finally, the displaced target DNA again hybridizes with the H1 and initiates cycle amplification...
January 1, 2018: Talanta
Kaustubh Shukla, Roshan Thakur, Debayan Ganguli, Desirazu Rao, Ganesh Nagaraju
G-quadruplex (G4) secondary structures have been implicated in various biological processes including gene expression, DNA replication and telomere maintenance. However, unresolved G4 structures impede replication progression which can lead to generation of DNA double-strand breaks and genome instability. Helicases have been shown to resolve G4 structures to facilitate faithful duplication of the genome. Escherichia coli UvrD (EcUvrD) helicase plays a crucial role in nucleotide excision repair, mismatch repair and in the regulation of homologous recombination...
September 15, 2017: Biochemical Journal
Chenguang Wang, Nan Cheng, Longjiao Zhu, Yuancong Xu, Kunlun Huang, Pengyu Zhu, Shuifang Zhu, Wei Fu, Wentao Xu
A colorimetric biosensor for DNA screening was designed based on the conformational changes of the horseradish peroxidase (HRP)-mimicking DNAzyme. The scheme of DNA biosensing was designed based on the base pairing of DNAzyme sequence to inhibit the formation of HRP-mimicking hemin/G-quadruplex structures in the process of amplification. DNA could be amplified via the universal primer multiplex polymerase chain reaction (UP-M-PCR) and innovatively detected as color disappear in the reaction visible to the naked eye...
September 22, 2017: Analytica Chimica Acta
María José Lista, Rodrigo Prado Martins, Gaelle Angrand, Alicia Quillévéré, Chrysoula Daskalogianni, Cécile Voisset, Marie-Paule Teulade-Fichou, Robin Fåhraeus, Marc Blondel
The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome replication and maintenance but also highly antigenic. Hence, EBV evolved a system in which the glycine-alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA at a minimal level to ensure its essential function thereby, at the same time, minimizing immune recognition. Defining intervention points where to interfere with EBNA1 immune evasion is an important step to trigger an immune response against EBV-carrying cancers...
August 31, 2017: Microbial Cell
Tabish Hussain, Dhurjhoti Saha, Gunjan Purohit, Anirban Kar, Anand Kishore Mukherjee, Shalu Sharma, Suman Sengupta, Parashar Dhapola, Basudeb Maji, Sreekanth Vedagopuram, Nobuko T Horikoshi, Nobuo Horikoshi, Raj K Pandita, Santanu Bhattacharya, Avinash Bajaj, Jean-François Riou, Tej K Pandita, Shantanu Chowdhury
We observed extra-telomeric binding of the telomere repeat binding factor TRF2 within the promoter of the cyclin-dependent kinase CDKNIA (p21/CIP1/WAF1). This result in TRF2 induced transcription repression of p21. Interestingly, p21 repression was through engagement of the REST-coREST-LSD1-repressor complex and altered histone marks at the p21 promoter in a TRF2-dependent fashion. Furthermore, mutational analysis shows p21 repression requires interaction of TRF2 with a p21 promoter G-quadruplex. Physiologically, TRF2-mediated p21 repression attenuated drug-induced activation of cellular DNA damage response by evading G2/M arrest in cancer cells...
September 14, 2017: Scientific Reports
Sofia Kolesnikova, Martin Hubálek, Lucie Bednárová, Josef Cvacka, Edward A Curtis
G-quadruplexes can multimerize under certain conditions, but the sequence requirements of such structures are not well understood. In this study, we investigated the ability of all possible variants of the central tetrad in a monomeric, parallel-strand G-quadruplex to form higher-order structures. Although most of these 256 variants existed primarily as monomers under the conditions of our screen, ∼10% formed dimers or tetramers. These structures could form in a wide range of monovalent and divalent metal ions, and folding was highly cooperative in both KCl and MgCl2...
September 6, 2017: Nucleic Acids Research
Felix Nußbaumer, Michael Andreas Juen, Catherina Gasser, Johannes Kremser, Thomas Müller, Martin Tollinger, Christoph Kreutz
We report the synthesis of atom-specifically 13C-modified building blocks that can be incorporated into DNA via solid phase synthesis to facilitate investigations on structural and dynamic features via NMR spectroscopy. In detail, 6-13C-modified pyrimidine and 8-13C purine DNA phosphoramidites were synthesized and incorporated into a polypurine tract DNA/RNA hybrid duplex to showcase the facile resonance assignment using site-specific labeling. We also addressed micro- to millisecond dynamics in the mini-cTAR DNA...
September 6, 2017: Nucleic Acids Research
Jose F Moruno-Manchon, Edward C Koellhoffer, Jayakrishnan Gopakumar, Shashank Hambarde, Nayun Kim, Louise D McCullough, Andrey S Tsvetkov
The G-quadruplex is a non-canonical DNA secondary structure formed by four DNA strands containing multiple runs of guanines. G-quadruplexes play important roles in DNA recombination, replication, telomere maintenance, and regulation of transcription. Small molecules that stabilize the G-quadruplexes alter gene expression in cancer cells. Here, we hypothesized that the G-quadruplexes regulate transcription in neurons. We discovered that pyridostatin, a small molecule that specifically stabilizes G-quadruplex DNA complexes, induced neurotoxicity and promoted the formation of DNA double-strand breaks (DSBs) in cultured neurons...
September 12, 2017: Aging
Alicia K Byrd, Kevin D Raney
Pif1 family helicases have multiple roles in the maintenance of nuclear and mitochondrial DNA in eukaryotes. Saccharomyces cerevisiae Pif1 is involved in replication through barriers to replication, such as G-quadruplexes and protein blocks, and reduces genetic instability at these sites. Another Pif1 family helicase in S. cerevisiae, Rrm3, assists in fork progression through replication fork barriers at the rDNA locus and tRNA genes. ScPif1 (Saccharomyces cerevisiae Pif1) also negatively regulates telomerase, facilitates Okazaki fragment processing, and acts with polymerase δ in break-induced repair...
September 12, 2017: Biochemical Society Transactions
Shuangyan Zhang, Qiong Wu, Hao Zhang, Qi Wang, Xicheng Wang, Wenjie Mei, Xiaohui Wu, Wenjie Zheng
Herein, two polypyridyl ruthenium(II) complexes with alkynes, [Ru(bpy)2L](ClO4)2 (L=p-TEPIP (1) and p-BEPIP (2); bpy=2,2'-bipyridine; p-TEPIP=2-(4-trimethylsilylpropargyl)-1H-imidazo[4,5f][1,10]phenanthroline; p-BEPIP=2-(4-phenyacetylenephenyl)-1H-imidazo[4,5f][1,10]phenanthroline) have been successfully achieved in yields of 32%-89% by a Sonogashira coupling reaction under microwave irradiation. We studied these complexes as potential stabilizers of c-myc G-quadruplex DNA. Observations revealed that both complexes could selectively bind to and stabilize c-myc G-quadruplex DNA with a constant of approximately 1...
August 30, 2017: Journal of Inorganic Biochemistry
Xiangzi Yao, Di Song, Tingxiao Qin, Chunfan Yang, Ze Yu, Xiaohong Li, Kunhui Liu, Hongmei Su
The interaction of ligands with G-quadruplexes has attracted considerable attention due to its importance in molecular recognition and anticancer drugs design. Here, we utilize triplet excited state as a sensitive reporter to study the binding interaction of zinc cationic porphyrin (ZnTMPyP4) with three G-quadruplexes, AG3(T2AG3)3, (G4T4G4)2, and (TG4T)4. By monitoring the triplet decay dynamics of ZnTMPyP4 with transient absorption spectroscopy, the coexisted binding modes via π-π stacking of porphyrin macrocycle and the G-quartets are allowed to be identified quantitatively, which involve intercalation (25% and 36%) versus end-stacking (75% and 64%) for AG3(T2AG3)3 and (G4T4G4)2, and end-stacking (23%) versus partial intercalation (77%) for (TG4T)4...
September 8, 2017: Scientific Reports
Kaili Yang, Min Huo, Yuehua Guo, Yizhuo Yang, Jie Wu, Lin Ding, Huangxian Ju
A target-induced cyclic strategy for DNAzyme formation was proposed to achieve simple, sensitive and universal detection of protein biomarkers with convenient colorimetric or chemiluminescence imaging readout. In the assay, the target protein was recognized by a pair of DNA-labeled antibodies (Ab1-DNA1 and Ab2-DNA2) to form a proximate complex, which could hybridize with the conjugate DNA3/DNA4 to release the guanine-rich DNA4 and thus formed G-quadruplex/hemin horseradish peroxidase-mimicking DNAzyme. The process could be further recycled with Exonuclease III by cleaving DNA3 to free the proximate complex, resulting in the cyclic formation of DNAzyme...
September 7, 2017: Analyst
Akiko Kumagai, William G Dunphy
Treslin, which is essential for incorporation of Cdc45 into the replicative helicase, possesses a partner called MTBP. We have analyzed Xenopus and human MTBP to assess its role in DNA replication. Depletion of MTBP from Xenopus egg extracts, which also removes Treslin, abolishes DNA replication. These extracts be can rescued with recombinant Treslin-MTBP, but not Treslin or MTBP alone. Thus, Treslin-MTBP is collectively necessary for replication. We have identified a C-terminal region of MTBP (the CTM domain) that binds efficiently to both double-stranded DNA and G-quadruplex (G4) DNA...
September 6, 2017: Molecular Biology of the Cell
Daxiu Li, Jiaqing Xie, Wenjiao Zhou, Bingying Jiang, Ruo Yuan, Yun Xiang
The determination of the level of Cu(2+) plays important roles in disease diagnosis and environmental monitoring. By coupling Cu(+)-catalyzed click chemistry and metal ion-dependent DNAzyme cyclic amplification, we have developed a convenient and sensitive colorimetric sensing method for the detection of Cu(2+) in human serums. The target Cu(2+) can be reduced by ascorbate to form Cu(+), which catalyzes the azide-alkyne cycloaddition between the azide- and alkyne-modified DNAs to form Mg(2+)-dependent DNAzymes...
September 4, 2017: Analytical and Bioanalytical Chemistry
Jinlong Li, Guangwu He, Chaoli Mu, Keming Wang, Yang Xiang
DNA methylation catalyzed by DNA methyltransferase plays an important role in many biological processes including gene transcription, genomic imprinting and cellular differentiation. Herein, a novel and effective electrochemical method for the assay of DNA methyltransferase 1(DNMT1) activity has been successfully developed by using uracil-specific excision reagent (USER) induced G-quadruplex formation. Briefly, double stranded DNA containing the recognition sequence of DNMT1 is immobilized on the electrode...
September 15, 2017: Analytica Chimica Acta
Giel P Göertz, Sandra R Abbo, Jelke J Fros, Gorben P Pijlman
Zika virus (ZIKV; family Flaviviridae; genus Flavivirus) is a pathogenic mosquito-borne RNA virus that currently threatens human health in the Americas, large parts of Asia and occasionally elsewhere in the world. ZIKV infection is often asymptomatic but can cause severe symptoms including congenital microcephaly and Guillain-Barré syndrome. The positive single-stranded RNA genome of the mosquito-borne ZIKV requires effective replication in two evolutionary distinct hosts - mosquitoes and primates. In addition to some of the viral proteins, the ZIKV genomic RNA and functional RNAs produced thereof aid in the establishment of productive infection and the evasion of host cell antiviral responses...
August 31, 2017: Virus Research
Souheila Amor, Sunny Y Yang, Judy M Y Wong, David Monchaud
G-quadruplexes (G4s) are higher-order nucleic acid structures that fold from guanine (G)-rich DNA and RNA strands. This field of research gains traction as a major chemical biology area since it aims at uncovering many key cellular mechanisms in which quadruplexes are involved. The wealth of knowledge acquired over the past three decades strongly supports pivotal roles of G4 in the regulation of gene expression at both transcriptional (DNA quadruplexes) and translational levels (RNA quadruplexes). Recent biochemical discoveries uncovered myriad of additional G4 actions: from chromosomal stability to the firing of replication origins, from telomere homeostasis to functional dysregulations underlying genetic diseases (including cancers and neurodegeneration)...
September 1, 2017: Current Protocols in Cell Biology
Gregory R Wiedman, Yanan Zhao, Arkady Mustaev, Jinglei Ping, Ramya Vishnubhotla, A T Charlie Johnson, David S Perlin
This technical report describes the development of an aptamer for sensing azole antifungal drugs during therapeutic drug monitoring. Modified synthetic evolution of ligands through exponential enrichment (SELEX) was used to discover a DNA aptamer recognizing azole class antifungal drugs. This aptamer undergoes a secondary structural change upon binding to its target molecule, as shown through fluorescence anisotropy-based binding measurements. Experiments using circular dichroism spectroscopy revealed a unique G-quadruplex structure that was essential and specific for binding to the azole antifungal target...
July 2017: MSphere
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