Helix Formation by Guanylic Acid

Gellert, Martin; Lipsett, Marie N.; Davies, David R.

doi:10.1073/pnas.48.12.2013

Cited by 1,389 publications

(991 citation statements)

References 5 publications

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“…Thus, even in the presence of the poly(C), which creates a large driving force for formation of the very stable poly(G).poly(C) structure, poly(G) persists in metastable, self-associated conformations to rather high temperatures. Guanine residues can aggregate into a number of structures, involving several possible base pairing schemes (Gellert et al, 1962;Pochon & Michelson, 1965;Chantot et al, 1971). One can devise G * G base pairs in which protons participate in H bonding and are thus essential for the G. G formation.…”

Section: (C) Metastable Quanine -Gumande Structures May Underlie the Hymentioning

confidence: 99%

Metastable secondary structures in ribosomal RNA molecular hysteresis in the acid-base titration of Escherichia coli ribosomal RNA

Revzin

Neumann

Katchalsky

1973

Journal of Molecular Biology

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The metastable conformational states which underlie the hysteresis displayed by Escherichia coli ribosomal RNA in its pH titration in the acid range have been analyzed in terms of acid-stable RNA secondary structures. Sedimentation measurements show that the phenomenon is ktramolecular, so that analysis of the hysteresis loops can, in principle, reveal details of molecular architecture. Hysteresis cycles obtained spectrophotometrically and potentiometrically were compared for RNA in solutions of different ionic strengths and ionic compositions. The effect is much smaller at lower ionic strength and disappears in the absence of magnesium ions. The curve followed upon addition of acid appears to reflect the equilibrium state of the system at each pH value. On the "base branch" of the loop, a slow absorbance change (complete in hours) was observed after the pH was raised by addition of a portion of base. This slow process is attributed to the annealing of "mismatched" multihelical regions of the ribosomal RNA. Certain regions, however, remain in metastable configurations for days and it is these long-lived non-equilibrium structures that underlie the hysteresis. Titration at 35°C gave hysteresis loops of the same size and shape as at 20°C ; indeed, we found that the metastabilities are not removed even at 80°C. Ultraviolet light absorbance difference spectra at 80°C between solutions at the same pH, but on different branches of the cycle, give insight into the nature of the metastable conformation(s).Our experimental observations lead us to propose that the hysteresis is due to the formation at acidic pH of double-helical structures involving protonated guanine and adenine base pairs. The G.G pairs seem especially important to account for the very high thermal stability, as well as for the fact that the structures formed at a given pH value as acid is added dissociate only at higher pH values when the solution is titrated with base. Titrations of transfer RNA, along with literature data on 16 S rRNA primary structure, imply that the metastable regions in rRNA may consist of perhaps 10 to 15 base pairs.

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Section: (C) Metastable Quanine -Gumande Structures May Underlie the Hymentioning

confidence: 99%

Metastable secondary structures in ribosomal RNA molecular hysteresis in the acid-base titration of Escherichia coli ribosomal RNA

Revzin

Neumann

Katchalsky

1973

Journal of Molecular Biology

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“…1a). While guanine-rich single-stranded DNA can readily adopt such a structure in vitro, its in vivo formation has remained a subject of debate ever since the structure was first described 1 . Recent years have, however, seen a greatly increased interest in G-quadruplexes due to new insights into their possible roles in various biological processes such as gene expression, epigenetic regulation, telomere maintenance and DNA replication initiation [2][3][4][5][6][7][8] .…”

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confidence: 99%

A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites

et al. 2014

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Genomes contain many sequences that are intrinsically difficult to replicate. Tracts of tandem guanines, for instance, have the potential to adopt stable G-quadruplex structures, which are prone to cause genome alterations. Here we describe G4 DNA-induced mutagenesis in Caenorhabditis elegans and identify a non-canonical DNA break repair mechanism that generates deletions characterized by an extremely narrow size distribution, minimal homology of exactly one nucleotide at the junctions, and by the occasional presence of templated insertions. This typical mutation profile is fully dependent on the A-family polymerase Theta, the absence of which leads to profound loss of sequences surrounding G4 motifs. Theta-mediated end-joining prevails over non-homologous end joining and homologous recombination and prevents genomic havoc at replication fork barriers at the expense of small deletions. G4 DNA-induced deletions also manifest in the genomes of wild isolates of C. elegans, indicating a protective role for this pathway during evolution.

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“…Recent mounting biological interest has driven attention to G-quadruplex (G4) (10-16), a four-stranded structure consisting of a stack of G-tetrad layers, each comprising four guanines Hoogsteen hydrogen-bonded in a coplanar arrangement (17). This helical structure with different possible orientations between the four strands is highly polymorphic (6,7,16,18,19), but so far, only right-handed forms have been observed.…”

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confidence: 99%

Structure of a left-handed DNA G-quadruplex

Chung

Heddi

Schmitt

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

119

166

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Aside from the well-known double helix, DNA can also adopt an alternative four-stranded structure known as G-quadruplex. Implications of such a structure in cellular processes, as well as its therapeutic and diagnostic applications, have been reported. The G-quadruplex structure is highly polymorphic, but so far, only right-handed helical forms have been observed. Here we present the NMR solution and X-ray crystal structures of a left-handed DNA G-quadruplex. The structure displays unprecedented features that can be exploited as unique recognition elements.G-quadruplex | left-handed helix | nucleic acid | NMR | X-ray crystallography

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Helix Formation by Guanylic Acid

Cited by 1,389 publications

References 5 publications

Metastable secondary structures in ribosomal RNA molecular hysteresis in the acid-base titration of Escherichia coli ribosomal RNA

Metastable secondary structures in ribosomal RNA molecular hysteresis in the acid-base titration of Escherichia coli ribosomal RNA

A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites

Structure of a left-handed DNA G-quadruplex

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