keyword
MENU ▼
Read by QxMD icon Read
search

Non canonical DNA

keyword
https://www.readbyqxmd.com/read/28934471/a-novel-non-canonical-pip-box-mediates-parg-interaction-with-pcna
#1
Tanja Kaufmann, Irina Grishkovskaya, Anton A Polyansky, Sebastian Kostrhon, Eva Kukolj, Karin M Olek, Sebastien Herbert, Etienne Beltzung, Karl Mechtler, Thomas Peterbauer, Josef Gotzmann, Lijuan Zhang, Markus Hartl, Bojan Zagrovic, Kareem Elsayad, Kristina Djinovic-Carugo, Dea Slade
Poly(ADP-ribose) glycohydrolase (PARG) regulates cellular poly(ADP-ribose) (PAR) levels by rapidly cleaving glycosidic bonds between ADP-ribose units. PARG interacts with proliferating cell nuclear antigen (PCNA) and is strongly recruited to DNA damage sites in a PAR- and PCNA-dependent fashion. Here we identified PARG acetylation site K409 that is essential for its interaction with PCNA, its localization within replication foci and its recruitment to DNA damage sites. We found K409 to be part of a non-canonical PIP-box within the PARG disordered regulatory region...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934470/monitoring-replication-protein-a-rpa-dynamics-in-homologous-recombination-through-site-specific-incorporation-of-non-canonical-amino-acids
#2
Nilisha Pokhrel, Sofia Origanti, Eric Parker Davenport, Disha Gandhi, Kyle Kaniecki, Ryan A Mehl, Eric C Greene, Chris Dockendorff, Edwin Antony
An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28921497/quantitative-analysis-of-nucleic-acid-stability-with-ligands-under-high-pressure-to-design-novel-drugs-targeting-g-quadruplexes
#3
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
https://www.readbyqxmd.com/read/28911096/distinct-regulation-of-alternative-polyadenylation-and-gene-expression-by-nuclear-poly-a-polymerases
#4
Weimin Li, Wencheng Li, Rakesh S Laishram, Mainul Hoque, Zhe Ji, Bin Tian, Richard A Anderson
Polyadenylation of nascent RNA by poly(A) polymerase (PAP) is important for 3' end maturation of almost all eukaryotic mRNAs. Most mammalian genes harbor multiple polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms with distinct functions. How poly(A) polymerases may regulate PAS usage and hence gene expression is poorly understood. Here, we show that the nuclear canonical (PAPα and PAPγ) and non-canonical (Star-PAP) PAPs play diverse roles in PAS selection and gene expression...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28906048/synthesis-of-rna-containing-5-hydroxymethyl-5-formyl-and-5-carboxycytidine
#5
Iacovos N Michaelides, Nobuhiro Tago, Bastien Viverge, Thomas Carell
5-Hydroxymethyl-, 5-formyl-, and 5-carboxycytidine are new epigenetic bases (hmdC, fdC, cadC) that were recently discovered in the DNA of higher eukaryotes. The same bases (hmC, fC and caC) have now also been detected in mammalian RNA with a high abundance in mRNA. While for the DNA bases phosphoramidites (PAs) are available that allow the synthesis of xdC-containing oligonucleotides for deeper biological studies, the corresponding RNA PAs for fC and caC have not yet been disclosed. Here we report novel RNA PAs for hmC, fC and caC that can be used in routine RNA synthesis...
September 14, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28904242/the-g-quadruplex-dna-stabilizing-drug-pyridostatin-promotes-dna-damage-and-downregulates-transcription-of-brca1-in-neurons
#6
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
https://www.readbyqxmd.com/read/28833137/tert-ezh2-network-regulates-lipid-metabolism-and-dna-damage-responses-in-glioblastoma
#7
Fahim Ahmad, Shruti Patrick, Touseef Sheikh, Vikas Sharma, Pankaj Pathak, Prit Benny Malgulwar, Anupam Kumar, Shanker Datt Joshi, Chitra Sarkar, Ellora Sen
Elevated expression of enhancer of zeste homolog 2 (EZH2) - a histone H3K27 methyltransferase was observed in gliomas harboring telomerase reverse transcriptase (TERT) promoter mutations. Given the known involvement of TERT and EZH2 in glioma progression, the co-relation between the two and subsequently its involvement in metabolic programming was investigated. Inhibition of hTERT either pharmacologically or through genetic manipulation not only decreased EZH2 expression, but also (i) abrogated FASN levels, (ii) decreased de novo fatty acid accumulation, and (iii) increased Ataxia-telangiectasia mutated (ATM) phosphorylation levels...
August 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28818035/comparative-analysis-of-inosine-substituted-duplex-dna-by-circular-dichroism-and-x-ray-crystallography
#8
Justin P Peters, Ewa A Kowal, Pradeep S Pallan, Martin Egli, L James Maher
Leveraging structural biology tools, we report the results of experiments seeking to determine if the different mechanical properties of DNA polymers with base analog substitutions can be attributed, at least in part, to induced changes from classical B-form DNA. The underlying hypothesis is that different inherent bending and twisting flexibilities may characterize non-canonical B-DNA, so that it is inappropriate to interpret mechanical changes caused by base analog substitution as resulting simply from 'electrostatic' or 'base stacking' influences without considering the larger context of altered helical geometry...
September 4, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28781234/structural-basis-for-the-canonical-and-non-canonical-pam-recognition-by-crispr-cpf1
#9
Takashi Yamano, Bernd Zetsche, Ryuichiro Ishitani, Feng Zhang, Hiroshi Nishimasu, Osamu Nureki
The RNA-guided Cpf1 (also known as Cas12a) nuclease associates with a CRISPR RNA (crRNA) and cleaves the double-stranded DNA target complementary to the crRNA guide. The two Cpf1 orthologs from Acidaminococcus sp. (AsCpf1) and Lachnospiraceae bacterium (LbCpf1) have been harnessed for eukaryotic genome editing. Cpf1 requires a specific nucleotide sequence, called a protospacer adjacent motif (PAM), for target recognition. Besides the canonical TTTV PAM, Cpf1 recognizes suboptimal C-containing PAMs. Here, we report four crystal structures of LbCpf1 in complex with the crRNA and its target DNA containing either TTTA, TCTA, TCCA, or CCCA as the PAM...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28765009/involvement-of-trnas-in-replication-of-human-mitochondrial-dna-and-modifying-effects-of-telomerase
#10
Meenakshisundaram Balasubramaniam, Robert J Shmookler Reis, Srinivas Ayyadevara, Xianwei Wang, Akshatha Ganne, Magomed Khaidakov
Overexpression of telomerase has been shown to significantly increase the lifespan of mice. When mechanistically attributed to repair of critically short telomeres, the lifespan extending action of telomerase cannot be reconciled with the observation that telomerase-null mice do not exhibit shortening of lifespan for at least two generations. We hypothesized that telomerase may interfere with replication of mitochondrial DNA (mtDNA) in a way that reduces formation of deletions - the primary cause of age-dependent cell attrition in non-renewable cells such as myocytes and neurons...
July 29, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28763217/characterization-of-g4-g4-crosstalk-in-the-c-kit-promoter-region
#11
Riccardo Rigo, Claudia Sissi
The proximal promoter of c-KIT contains a peculiar domain that consists of three short G-rich sequences that are close together and can fold into noncanonical DNA secondary structures called G-quadruplexes (G4). Here, we focused on a sequence containing two consecutive G4 (kit2 and kit*). By electrophoretic, surface plasmon resonance, and spectroscopic techniques, we demonstrated that they retain the ability to fold into G4 upon being inserted into the extended sequence. Here, we highlighted the occurrence of crosstalk between the two forming units...
August 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28758290/crystal-structure-of-master-biofilm-regulator-csgd-regulatory-domain-reveals-an-atypical-receiver-domain
#12
Yurong Wen, Zhenlin Ouyang, Bart Devreese, Wangxiao He, Yongping Shao, Wuyuan Lu, Fang Zheng
The master regulator CsgD switches planktonic growth to biofilm formation by activating synthesis of curli fimbriae and cellulose in Enterobacteriaceae. CsgD was classified to be the LuxR response regulatory family, while its cognate sensor histidine kinase has not been identified yet. CsgD consists of a C-terminal DNA binding domain and an N-terminal regulatory domain that provokes the upstream signal transduction to further modulate its function. We provide the crystal structure of Salmonella Typhimurium CsgD regulatory domain, which reveals an atypical β5α5 response regulatory receiver domain folding with the α2 helix representing as a disorder loop compared to the LuxR/FixJ canonical response regulator, and the structure indicated a noteworthy α5 helix similar to the non-canonical master regulator VpsT receiver domain α6...
July 30, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28754468/microhomology-mediated-end-joining-good-bad-and-ugly
#13
REVIEW
Ja-Hwan Seol, Eun Yong Shim, Sang Eun Lee
DNA double-strand breaks (DSBs) are induced by a variety of genotoxic agents, including ionizing radiation and chemotherapy drugs for treating cancers. The elimination of DSBs proceeds via distinctive error-free and error-prone pathways. Repair by homologous recombination (HR) is largely error-free and mediated by RAD51/BRCA2 gene products. Classical non-homologous end joining (C-NHEJ) requires the Ku heterodimer and can efficiently rejoin breaks, with occasional loss or gain of DNA information. Recently, evidence has unveiled another DNA end-joining mechanism that is independent of recombination factors and Ku proteins, termed alternative non-homologous end joining (A-NHEJ)...
July 16, 2017: Mutation Research
https://www.readbyqxmd.com/read/28740723/at-the-interface-of-three-nucleic-acids-the-role-of-rna-binding-proteins-and-poly-adp-ribose-in-dna-repair
#14
E E Alemasova, O I Lavrik
RNA-binding proteins (RBPs) regulate RNA metabolism, from synthesis to decay. When bound to RNA, RBPs act as guardians of the genome integrity at different levels, from DNA damage prevention to the post-transcriptional regulation of gene expression. Recently, RBPs have been shown to participate in DNA repair. This fact is of special interest as DNA repair pathways do not generally involve RNA. DNA damage in higher organisms triggers the formation of the RNA-like polymer - poly(ADP-ribose) (PAR). Nucleic acid-like properties allow PAR to recruit DNA- and RNA-binding proteins to the site of DNA damage...
April 2017: Acta Naturae
https://www.readbyqxmd.com/read/28729824/mouse-models-of-c9orf72-hexanucleotide-repeat-expansion-in-amyotrophic-lateral-sclerosis-frontotemporal-dementia
#15
REVIEW
Ranjan Batra, Chris W Lee
The presence of hexanucleotide repeat expansion (HRE) in the first intron of the human C9orf72 gene is the most common genetic cause underlying both familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies aimed at elucidating the pathogenic mechanisms associated of C9orf72 FTD and ALS (C9FTD/ALS) have focused on the hypothesis of RNA and protein toxic gain-of-function models, including formation of nuclear RNA foci containing GGGGCC (G4C2) HRE, inclusions containing dipeptide repeat proteins through a non-canonical repeat associated non-ATG (RAN) translation mechanism, and on loss-of-function of the C9orf72 protein...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28728523/structural-insights-into-the-binding-of-small-ligand-molecules-to-a-g-quadruplex-dna-located-in-the-hiv-1-promoter
#16
Petar M Mitrasinovic
Targeting guanine (G)-rich DNA sequences, folded into non-canonical G-quadruplex (G4) structures, by small ligand molecules is a promising strategy for gene therapy of various diseases. There is experimental proposal that, among eight studied ligands, nitidine chloride - NC and a benzo phenanthridine derivative - BPD have the highest binding affinities for such a sequence (5'-T(1)G(2)G(3)C(4)C(5)T(6)G(7)G(8)G(9)C(10)G(11)G(12)G(13)A(14)C(15)T(16)G(17)G(18)G(19)-3') in the HIV-1 promoter, indicating that an anti-HIV-1 prodrug may regulate the expression of the promoter...
July 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28719624/sequence-specific-dna-binding-by-myc-max-to-low-affinity-non-e-box-motifs
#17
Michael Allevato, Eugene Bolotin, Mark Grossman, Daniel Mane-Padros, Frances M Sladek, Ernest Martinez
The MYC oncoprotein regulates transcription of a large fraction of the genome as an obligatory heterodimer with the transcription factor MAX. The MYC:MAX heterodimer and MAX:MAX homodimer (hereafter MYC/MAX) bind Enhancer box (E-box) DNA elements (CANNTG) and have the greatest affinity for the canonical MYC E-box (CME) CACGTG. However, MYC:MAX also recognizes E-box variants and was reported to bind DNA in a "non-specific" fashion in vitro and in vivo. Here, in order to identify potential additional non-canonical binding sites for MYC/MAX, we employed high throughput in vitro protein-binding microarrays, along with electrophoretic mobility-shift assays and bioinformatic analyses of MYC-bound genomic loci in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28717872/stress-induced-changes-in-mirna-biogenesis-and-functioning
#18
REVIEW
Marta Olejniczak, Anna Kotowska-Zimmer, Wlodzimierz Krzyzosiak
MicroRNAs (miRNAs) are small, noncoding RNAs that play key roles in the regulation of cellular homeostasis in eukaryotic organisms. There is emerging evidence that some of these processes are influenced by various forms of cellular stresses, including DNA damage, pathogen invasion or chronic stress associated with diseases. Many reports over the last decade demonstrate examples of stress-induced miRNA deregulation at the level of transcription, processing, subcellular localization and functioning. Moreover, core miRNA biogenesis proteins and their interactions with partners can be selectively regulated in response to stress signaling...
July 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28714476/modulation-of-nongenomic-activation-of-pi3k-signalling-by-tetramerization-of-n-terminally-cleaved-rxr%C3%AE
#19
Liqun Chen, Alexander E Aleshin, Gulimiran Alitongbieke, Yuqi Zhou, Xindao Zhang, Xiaohong Ye, Mengjie Hu, Gaoang Ren, Ziwen Chen, Yue Ma, Duo Zhang, Shuai Liu, Weiwei Gao, Lijun Cai, Lingjuan Wu, Zhiping Zeng, Fuquan Jiang, Jie Liu, Hu Zhou, Gregory Cadwell, Robert C Liddington, Ying Su, Xiao-Kun Zhang
Retinoid X receptor-alpha (RXRα) binds to DNA either as homodimers or heterodimers, but it also forms homotetramers whose function is poorly defined. We previously discovered that an N-terminally-cleaved form of RXRα (tRXRα), produced in tumour cells, activates phosphoinositide 3-kinase (PI3K) signalling by binding to the p85α subunit of PI3K and that K-80003, an anti-cancer agent, inhibits this process. Here, we report through crystallographic and biochemical studies that K-80003 binds to and stabilizes tRXRα tetramers via a 'three-pronged' combination of canonical and non-canonical mechanisms...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28687761/inactivation-of-pol-%C3%AE-and-c-nhej-eliminates-off-target-integration-of-exogenous-dna
#20
Alex N Zelensky, Joost Schimmel, Hanneke Kool, Roland Kanaar, Marcel Tijsterman
Off-target or random integration of exogenous DNA hampers precise genomic engineering and presents a safety risk in clinical gene therapy strategies. Genetic definition of random integration has been lacking for decades. Here, we show that the A-family DNA polymerase θ (Pol θ) promotes random integration, while canonical non-homologous DNA end joining plays a secondary role; cells double deficient for polymerase θ and canonical non-homologous DNA end joining are devoid of any integration events, demonstrating that these two mechanisms define random integration...
July 7, 2017: Nature Communications
keyword
keyword
46488
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"