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Non canonical DNA

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https://www.readbyqxmd.com/read/29351914/high-resolution-transcription-maps-reveal-the-widespread-impact-of-roadblock-termination-in-yeast
#1
Tito Candelli, Drice Challal, Jean-Baptiste Briand, Jocelyne Boulay, Odil Porrua, Jessie Colin, Domenico Libri
Transcription termination delimits transcription units but also plays important roles in limiting pervasive transcription. We have previously shown that transcription termination occurs when elongating RNA polymerase II (RNAPII) collides with the DNA-bound general transcription factor Reb1. We demonstrate here that many different DNA-binding proteins can induce termination by a similar roadblock (RB) mechanism. We generated high-resolution transcription maps by the direct detection of RNAPII upon nuclear depletion of two essential RB factors or when the canonical termination pathways for coding and non-coding RNAs are defective...
January 19, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29351274/dna-polymerase-iv-primarily-operates-outside-of-dna-replication-forks-in-escherichia-coli
#2
Sarah S Henrikus, Elizabeth A Wood, John P McDonald, Michael M Cox, Roger Woodgate, Myron F Goodman, Antoine M van Oijen, Andrew Robinson
In Escherichia coli, damage to the chromosomal DNA induces the SOS response, setting in motion a series of different DNA repair and damage tolerance pathways. DNA polymerase IV (pol IV) is one of three specialised DNA polymerases called into action during the SOS response to help cells tolerate certain types of DNA damage. The canonical view in the field is that pol IV primarily acts at replisomes that have stalled on the damaged DNA template. However, the results of several studies indicate that pol IV also acts on other substrates, including single-stranded DNA gaps left behind replisomes that re-initiate replication downstream of a lesion, stalled transcription complexes and recombination intermediates...
January 19, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29339157/drastic-stability-change-of-x-x-mismatch-in-d-cxg-trinucleotide-repeat-disorders-under-molecular-crowding-condition
#3
Ye Teng, Smritimoy Pramanik, Hisae Tateishi-Karimata, Tatsuya Ohyama, Naoki Sugimoto
The trinucleotide repeat d(CXG) (X = A, C, G or T) is the most common sequence causing repeat expansion disorders. The formation of non-canonical structures, such as hairpin structures with X-X mismatches, has been proposed to affect gene expression and regulation, which are important in pathological studies of these devastating neurological diseases. However, little information is available regarding the thermodynamics of the repeat sequence under crowded cellular conditions where many non-canonical structures such as G-quadruplexes are highly stabilized, while duplexes are destabilised...
January 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29327716/genomic-heterogeneity-of-alk-fusion-breakpoints-in-non-small-cell-lung-cancer
#4
Jason N Rosenbaum, Ryan Bloom, Jason T Forys, Jeff Hiken, Jon R Armstrong, Julie Branson, Samantha McNulty, Priya D Velu, Kymberlie Pepin, Haley Abel, Catherine E Cottrell, John D Pfeifer, Shashikant Kulkarni, Ramaswamy Govindan, Eric Q Konnick, Christina M Lockwood, Eric J Duncavage
In lung adenocarcinoma, canonical EML4-ALK inversion results in a fusion protein with a constitutively active ALK kinase domain. Evidence of ALK rearrangement occurs in a minority (2-7%) of lung adenocarcinoma, and only ~60% of these patients will respond to targeted ALK inhibition by drugs such as crizotinib and ceritinib. Clinically, targeted anti-ALK therapy is often initiated based on evidence of an ALK genomic rearrangement detected by fluorescence in situ hybridization (FISH) of interphase cells in formalin-fixed, paraffin-embedded tissue sections...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29320735/rybp-is-a-k63-ubiquitin-chain-binding-protein-that-inhibits-homologous-recombination-repair
#5
Mohammad A M Ali, Hilmar Strickfaden, Brian L Lee, Leo Spyracopoulos, Michael J Hendzel
Ring1-YY1-binding protein (RYBP) is a member of the non-canonical polycomb repressive complex 1 (PRC1), and like other PRC1 members, it is best described as a transcriptional regulator. However, several PRC1 members were recently shown to function in DNA repair. Here, we report that RYBP preferentially binds K63-ubiquitin chains via its Npl4 zinc finger (NZF) domain. Since K63-linked ubiquitin chains are assembled at DNA double-strand breaks (DSBs), we examined the contribution of RYBP to DSB repair. Surprisingly, we find that RYBP is K48 polyubiquitylated by RNF8 and rapidly removed from chromatin upon DNA damage by the VCP/p97 segregase...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29301210/design-synthesis-and-biological-evaluation-of-new-substituted-diquinolinyl-pyridine-ligands-as-anticancer-agents-by-targeting-g-quadruplex
#6
Rabindra Nath Das, Edith Chevret, Vanessa Desplat, Sandra Rubio, Jean-Louis Mergny, Jean Guillon
G-quadruplexes (G4) are stacked non-canonical nucleic acid structures found in specific G-rich DNA or RNA sequences in the human genome. G4 structures are liable for various biological functions; transcription, translation, cell aging as well as diseases such as cancer. These structures are therefore considered as important targets for the development of anticancer agents. Small organic heterocyclic molecules are well known to target and stabilize G4 structures. In this article, we have designed and synthesized 2,6-di-(4-carbamoyl-2-quinolyl)pyridine derivatives and their ability to stabilize G4-structures have been determined through the FRET melting assay...
December 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29287594/comprehensive-molecular-biomarker-identification-in-breast-cancer-brain-metastases
#7
Hans-Juergen Schulten, Mohammed Bangash, Sajjad Karim, Ashraf Dallol, Deema Hussein, Adnan Merdad, Fatma K Al-Thoubaity, Jaudah Al-Maghrabi, Awatif Jamal, Fahad Al-Ghamdi, Hani Choudhry, Saleh S Baeesa, Adeel G Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Breast cancer brain metastases (BCBM) develop in about 20-30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques. METHODS: We compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p < 0...
December 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29284393/the-interplay-between-g-quadruplex-and-transcription
#8
Nayun Kim
G4 DNA is a non-canonical DNA structure consisting of a stacked array of G-quartets held together by base pairing between guanine bases. The formation of G4 DNA requires a cluster of guanine-runs within a strand of DNA. Even though the chemistry of this remarkable DNA structure has been under investigation for decades, evidence supporting the biological relevance of G4 DNA has only begun to emerge and point to very important and conserved biological functions. This review will specifically focus on the interplay between transcription and G4 DNA and discuss two alternative but interconnected perspectives...
December 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29280735/decoding-the-centromeric-nucleosome-through-cenp-n
#9
Satyakrishna Pentakota, Keda Zhou, Charlotte Smith, Stefano Maffini, Arsen Petrovic, Garry P Morgan, John R Weir, Ingrid R Vetter, Andrea Musacchio, Karolin Luger
Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A...
December 27, 2017: ELife
https://www.readbyqxmd.com/read/29280173/7-hydroxy-staurosporine-ucn-01-induces-dna-damage-response-and-autophagy-in-human-osteosarcoma-u2-os-cells
#10
Wei-Chih Lien, Ting-Yu Chen, Shi-Yuan Sheu, Tzu-Chien Lin, Fu-Chi Kang, Chung-Hsing Yu, Ta-Shen Kuan, Bu-Miin Huang, Chia-Yih Wang
Human osteosarcoma (bone cancer) is a highly malignant and the most prevalent bone tumor affecting children. Despite recent advances in the understanding of the molecular mechanism by which anticancer drugs kill osteosarcoma or block its growth, however, the mortality rate has declined only modestly. Thus, a new therapeutic approach is needed to be established. 7-hydroxystaurosporine, UCN-01, abrogates the G2 checkpoint thus enhancing the cytotoxicity of chemotherapeutic agents. In addition, it has been evaluated in clinical trials as a single antineoplastic agent in treating several cancers...
December 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29249801/foxc1-induced-non-canonical-wnt5a-mmp7-signaling-regulates-invasiveness-in-triple-negative-breast-cancer
#11
Bingchen Han, Bo Zhou, Ying Qu, Bowen Gao, Yali Xu, Stacey Chung, Hisashi Tanaka, Wei Yang, Armando E Giuliano, Xiaojiang Cui
Triple-negative breast cancer (TNBC) has high rates of local recurrence and distant metastasis, partially due to its high invasiveness. The Forkhead box C1 (FOXC1) transcription factor has been shown to be specifically overexpressed in TNBC and associated with poor clinical outcome. How TNBC's high invasiveness is driven by FOXC1 and its downstream targets remains poorly understood. In the present study, pathway-specific PCR array assays revealed that WNT5A and matrix metalloproteinase-7 (MMP7) were upregulated by FOXC1 in TNBC cells...
December 18, 2017: Oncogene
https://www.readbyqxmd.com/read/29247826/cytostatic-hydroxycoumarin-ot52-induces-er-golgi-stress-and-stat3-inhibition-triggering-non-canonical-cell-death-and-synergy-with-bh3-mimetics-in-lung-cancer
#12
Jin-Young Lee, Oualid Talhi, Dongman Jang, Claudia Cerella, Anthoula Gaigneaux, Kyu-Won Kim, Jung Weon Lee, Mario Dicato, Khaldoun Bachari, Byung Woo Han, Artur M S Silva, Barbora Orlikova, Marc Diederich
Coumarins are natural compounds with antioxidant, anti-inflammatory and anti-cancer potential known to modulate inflammatory pathways. Here, non-toxic biscoumarin OT52 strongly inhibited proliferation of non-small cell lung cancer cells with KRAS mutations, inhibited stem-like characteristics by reducing aldehyde dehydrogenase expression and abrogated spheroid formation capacity. This cytostatic effect was characterized by cell cycle arrest and onset of senescence concomitant with endoplasmic reticulum and Golgi stress, leading to metabolic alterations...
December 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29238697/ataxia-telangiectasia-mutated-modulation-of-carbon-metabolism-in-cancer
#13
REVIEW
Erika S Dahl, Katherine M Aird
The ataxia-telangiectasia mutated (ATM) protein kinase has been extensively studied for its role in the DNA damage response and its association with the disease ataxia telangiectasia. There is increasing evidence that ATM also plays an important role in other cellular processes, including carbon metabolism. Carbon metabolism is highly dysregulated in cancer due to the increased need for cellular biomass. A number of recent studies report a non-canonical role for ATM in the regulation of carbon metabolism. This review highlights what is currently known about ATM's regulation of carbon metabolism, the implication of these pathways in cancer, and the development of ATM inhibitors as therapeutic strategies for cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29238067/alternative-nhej-pathway-proteins-as-components-of-mycn-oncogenic-activity-in-human-neural-crest-stem-cell-differentiation-implications-for-neuroblastoma-initiation
#14
Erika A Newman, Sahiti Chukkapalli, Daniela Bashllari, Tina T Thomas, Raelene A Van Noord, Elizabeth R Lawlor, Mark J Hoenerhoff, Anthony W Opipari, Valerie P Opipari
Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Our previous work discovered a survival mechanism by which MYCN-amplified neuroblastoma circumvents cell death by upregulating components of the error-prone non-canonical alternative nonhomologous end-joining (alt-NHEJ) DNA repair pathway...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29228337/triplex-forming-oligonucleotides-a-third-strand-for-dna-nanotechnology
#15
Arun Richard Chandrasekaran, David A Rusling
DNA self-assembly has proved to be a useful bottom-up strategy for the construction of user-defined nanoscale objects, lattices and devices. The design of these structures has largely relied on exploiting simple base pairing rules and the formation of double-helical domains as secondary structural elements. However, other helical forms involving specific non-canonical base-base interactions have introduced a novel paradigm into the process of engineering with DNA. The most notable of these is a three-stranded complex generated by the binding of a third strand within the duplex major groove, generating a triple-helical ('triplex') structure...
December 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29226453/silver-i-mediated-base-pairs-in-dna-sequences-containing-7-deazaguanine-cytosine-base-pairs-towards-dna-with-entirely-metallated-watson-crick-base-pairs
#16
José M Méndez-Arriaga, Carmen R Maldonado, José A Dobado, Miguel A Galindo
DNA sequences comprising non-canonical 7-deazaguanine (7CG) and canonical cytosine (C) are capable of forming Watson-Crick base pairs via hydrogen bonds as well as silver(I)-mediated base pairs by coordination to central silver(I) ions. Duplex I and II containing 7CG and C have been synthesized and characterized. The incorporation of silver(I) ions into these duplexes has been studied by means of temperature-dependent UV-spectroscopy, circular dichroism and DFT calculations. The results suggest the formation of DNA molecules comprising contiguous metallated 7CG-AgI-C Watson-Crick base pairs that preserve the original B-type conformation...
December 10, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29222118/purine-and-pyrimidine-triple-helix-forming-oligonucleotides-recognize-qualitatively-different-target-sites-at-the-ribosomal-dna-locus
#17
Rodrigo Maldonado, Michael Filarsky, Ingrid Grummt, Gernot Längst
Triplexes are non-canonical DNA structures, which are functionally associated with regulation of gene expression through ncRNA targeting to chromatin. Based on the rules of Hoogsteen base pairing, poly-purine sequences of a duplex can potentially form triplex structures with single-stranded oligonucleotides. Prediction of triplex-forming sequences by bioinformatics analyses have revealed enrichment of potential triplex targeting sites (TTS) at regulatory elements, mainly in promoters and enhancers, suggesting a potential function of RNA-DNA triplexes in transcriptional regulation...
December 8, 2017: RNA
https://www.readbyqxmd.com/read/29211802/hidden-%C3%AE-helical-propensity-segments-within-disordered-regions-of-the-transcriptional-activator-chop
#18
Ángeles Canales, Marcel Rösinger, Javier Sastre, Isabella C Felli, Jesús Jiménez-Barbero, Guillermo Giménez-Gallego, Carlos Fernández-Tornero
C/EBP-homologous protein (CHOP) is a key determinant of the apoptotic response to endoplasmic reticulum stress or DNA damage. As a member of the C/EBP family, CHOP contains a low complexity N-terminal region involved in transcriptional activation, followed by a bZIP that binds DNA after dimerization. However, in contrast to other C/EBPs, CHOP directs binding to non-canonical C/EBP sites due to unique substitutions in its DNA-binding domain. Herein, we show that the N-terminal region of CHOP is intrinsically unstructured but contains two segments presenting α-helical propensity...
2017: PloS One
https://www.readbyqxmd.com/read/29190084/acovenoside-a-induces-mitotic-catastrophe-followed-by-apoptosis-in-non-small-cell-lung-cancer-cells
#19
Menna El Gaafary, Shahira M Ezzat, Abeer M El Sayed, Omar M Sabry, Susanne Hafner, Sophia Lang, Michael Schmiech, Tatiana Syrovets, Thomas Simmet
We investigated the cytotoxic potential of the cardenolide glycoside acovenoside A against non-small-cell lung cancer cells. Lung cancer is the leading cause of cancer-related mortality and the second most common cancer diagnosed. Epidemiological studies revealed a direct correlation between the regular administration of cardiac glycosides and a lower incidence of various cancers. Acovenoside A, isolated from the pericarps of Acokanthera oppositifolia, potently inhibited proliferation and induced cytotoxicity in A549 non-small-cell lung cancer cells with an IC50 of 68 ± 3 nM after 48 h of exposure...
November 30, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29189780/a-semi-synthetic-organism-that-stores-and-retrieves-increased-genetic-information
#20
Yorke Zhang, Jerod L Ptacin, Emil C Fischer, Hans R Aerni, Carolina E Caffaro, Kristine San Jose, Aaron W Feldman, Court R Turner, Floyd E Romesberg
Since at least the last common ancestor of all life on Earth, genetic information has been stored in a four-letter alphabet that is propagated and retrieved by the formation of two base pairs. The central goal of synthetic biology is to create new life forms and functions, and the most general route to this goal is the creation of semi-synthetic organisms whose DNA harbours two additional letters that form a third, unnatural base pair. Previous efforts to generate such semi-synthetic organisms culminated in the creation of a strain of Escherichia coli that, by virtue of a nucleoside triphosphate transporter from Phaeodactylum tricornutum, imports the requisite unnatural triphosphates from its medium and then uses them to replicate a plasmid containing the unnatural base pair dNaM-dTPT3...
November 29, 2017: Nature
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