Abstract C‐rich DNA has the capacity to form a tetra‐stranded structure known as an i‐motif. The i‐motifs within genomic have been proposed contribute regulation of transcription. However, direct experimental evidence for existence these structures in vivo missing. Whether i‐motif complex environment living cells is not currently known. Herein, using state‐of‐the‐art in‐cell NMR spectroscopy, we evaluate stabilities cellular environment. We show that formed from naturally occurring sequences...

We have synthesized, separated, and purified approximately 10 mg of a deoxyundecanucleotide duplex containing single centrally positioned covalent adduct between (+)-anti-benzo[a]pyrene (BP) diol epoxide the exocyclic amino group guanosine. Excellent proton NMR spectra are observed for (+)-trans-anti-BP epoxide-N2-dG opposite dC flanked by G.C pairs in d[C1-C2-A3-T4-C5-(BP)G6-C7-T8-A9-C10-C11].d[12- G13-T14-A15-G16-C17-G18-A19-T20-G 21-G22] +ADdesignated (BP)G.C 11-mer+BD. determined...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolution conformation of the (+)-cis-anti-[BP]dG adduct in a DNA duplex: Intercalation covalently attached benzo[a]pyrenyl ring into helix and displacement modified deoxyguanosineMonique Cosman, Carlos de los Santos, Radovan Fiala, Brian E. Hingerty, Victor Ibanez, Ernestina Luna, Ronald Harvey, Nicholas Geacintov, Suse Broyde, Dinshaw J. PatelCite this: Biochemistry 1993, 32, 16, 4145–4155Publication Date (Print):April 27, 1993Publication History...

Studies on DNA–ligand interactions in the cellular environment are problematic due to lack of suitable biophysical tools. To address this need, we developed an in-cell NMR-based approach for monitoring inside nuclei living human cells. Our method relies acquisition NMR data from cells electroporated with preformed complexes. The impact intracellular integrity complexes is assessed based signals unbound and ligand-bound forms a given DNA target. This technique was tested two model fragments...

In this study, we report the first atomic resolution structure of a stable G-hairpin formed by natively occurring DNA sequence. An 11-nt long G-rich oligonucleotide, 5′-d(GTGTGGGTGTG)-3′, corresponding to most abundant sequence motif in irregular telomeric from Saccharomyces cerevisiae (yeast), is demonstrated adopt novel type mixed parallel/antiparallel fold-back structure, which stabilized dynamic G:G base pairs that transit between N1-carbonyl symmetric and N1-carbonyl, N7-amino...

Mithramycin (MTH) is a DNA-binding antitumor agent containing A-B disaccharide and C-D-E trisaccharide segments projecting from opposite ends of an aglycone chromophore. We have previously reported on the solution structure MTH-DNA 6-mer complex based combined NMR molecular dynamics study. This study established that Mg2+-coordinated mithramycin dimer bound to widened minor groove centered about sequence-specific (G-C)·(G-C) site individual monomers were directed towards helix spanning six...

The transcription factor ASCIZ (ATMIN, ZNF822) has an unusually high number of recognition motifs for the product its main target gene, hub protein LC8 (DYNLL1). Using a combination biophysical methods, structural analysis by NMR and electron microscopy, cellular assays, we developed model that proposes concerted role intrinsic disorder multiple binding events in regulating transcription. We demonstrate long intrinsically disordered C-terminal domain binds to form dynamic ensemble complexes...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolution Conformation of the (-)-trans-anti-Benzo[c]phenanthrene-dA ([BPh]dA) Adduct opposite dT in a DNA Duplex: Intercalation Covalently Attached Benzo[c]phenanthrenyl Ring to 3'-Side Site and Comparison with (+)-trans-anti-[BPh]dA StereoisomerMonique Cosman, Alfred Laryea, Radovan Fiala, Brian E. Hingerty, Shantu Amin, Nicholas Geacintov, Suse Broyde, Dinshaw J. PatelCite this: Biochemistry 1995, 34, 4, 1295–1307Publication Date (Print):January...

Mitomycin C (MC) is a potent antitumor antibiotic which alkylates DNA through covalent linkage of its C-1″ position with the exocyclic N2amino group guanine to yield [MC]dG adduct at duplex level. We report on solution structure monoalkylated MC-DNA 9-mer complex where [MC]dG5 positioned opposite dLC14 in d(A3-C4-[MC]G5-T6).d(A13-C14-G15-T16) sequence context. The was solved based combined NMR-molecular dynamics study including NOE intensity refinement. formation occurs retention...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolution conformation of the (+)-trans-anti-[BPh]dA adduct opposite dT in a DNA duplex: Intercalation covalently attached benzo[c]phenanthrene to 5'-side site without disruption modified base pairMonique Cosman, Radovan Fiala, Brian E. Hingerty, Alfred Laryea, Hongmee Lee, Ronald G. Harvey, Shantu Amin, Nicholas Geacintov, Suse Broyde, and Dinshaw PatelCite this: Biochemistry 1993, 32, 46, 12488–12497Publication Date (Print):November 1,...

Abasic (AP) lesions are the most frequent type of damages occurring in cellular DNA. Here we describe conformational effects AP sites substituted for 2'-deoxyadenosine first (ap7), second (ap13) or third (ap19) loop quadruplex formed K(+) by human telomere DNA 5'-d[AG3(TTAG3)3]. CD spectra and electrophoresis reveal that presence does not hinder formation intramolecular quadruplexes. NMR show structural heterogeneity is substantially reduced ap7 ap19 as compared to wild-type. These two (ap7...

Ionizing radiation produces clustered damage to DNA which is difficult repair and thus more harmful than single lesions. Clustered lesions have only been investigated in dsDNA models. Introducing the term 'clustered G-quadruplexes' we report here on structural effects of multiple tetrahydrofuranyl abasic sites replacing loop adenines (A/AP) tetrad guanines (G/AP) quadruplexes formed by human telomere d[AG3(TTAG3)3] (htel-22) d[TAG3(TTAG3)3TT] (htel-25) K+ solutions. Single triple A/APs...

There are two basic mechanisms that associated with the maintenance of telomere length, which endows cancer cells unlimited proliferative potential. One mechanism, referred to as alternative lengthening telomeres (ALT), accounts for approximately 10–15% all human cancers. Tumours engaged in ALT pathway characterised by presence single stranded 5′-C-rich telomeric overhang (C-overhang). This recently identified hallmark cancers distinguishes them from healthy tissues and renders C-overhang a...

Abstract C‐rich DNA has the capacity to form a tetra‐stranded structure known as an i‐motif. The i‐motifs within genomic have been proposed contribute regulation of transcription. However, direct experimental evidence for existence these structures in vivo missing. Whether i‐motif complex environment living cells is not currently known. Herein, using state‐of‐the‐art in‐cell NMR spectroscopy, we evaluate stabilities cellular environment. We show that formed from naturally occurring sequences...

We report below on the NMR structural characterization of complex between AMP and a 40-mer RNA aptamer in aqueous solution. Resonance assignments are based multinuclear multidimensional studies complexes uniformly 13C,15N-labeled with either or aptamer. binds to an internal loop (labeled G7-G8-A9-A10-G11-A12-A13-A14-C15-U16-G17) bulge (G34 positioned opposite loop) segment aptamer, our study provides insights into features folding topology molecular recognition events binding pocket RNA....

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDirect Correlation of Exchangeable and Nonexchangeable Protons on Purine Bases in 13C,15N-Labeled RNA Using a HCCNH-TOCSY ExperimentRadovan Fiala, Feng Jiang, Dinshaw J. PatelView Author Information Cellular Biochemistry & Biophysics Program Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, 10021Cite this: Am. Chem. Soc. 1996, 118, 3, 689–690Publication Date (Web):January 24, 1996Publication History Received3 October...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolution Conformation of the (+)-cis-anti-[BP]dG Adduct Opposite a Deletion Site in DNA Duplex: Intercalation Covalently Attached Benzo[a]pyrene into Helix with Base Displacement Modified Deoxyguanosine Minor GrooveMonique Cosman, Radovan Fiala, Brian E. Hingerty, Shantu Amin, Nicholas Geacintov, Suse Broyde, and Dinshaw J. PatelCite this: Biochemistry 1994, 33, 38, 11518–11527Publication Date (Print):September 27, 1994Publication History Published...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolution Conformation of the (+)-trans-anti-[BP]dG Adduct Opposite a Deletion Site in DNA Duplex: Intercalation Covalently Attached Benzo[a]pyrene into Helix with Base Displacement Modified Deoxyguanosine Major GrooveMonique Cosman, Radovan Fiala, Brian E. Hingerty, Shantu Amin, Nicholas Geacintov, Suse Broyde, and Dinshaw J. PatelCite this: Biochemistry 1994, 33, 38, 11507–11517Publication Date (Print):September 27, 1994Publication History...