Encoding canonical DNA quadruplex structure (original) (raw)
Related papers
Existence and consequences of G-quadruplex structures in DNA
While the discovery of B-form DNA 60 years ago has defined our molecular view of the genetic code, other postulated DNA secondary structures, such as A-DNA, Z-DNA, H-DNA, cruciform and slipped structures have provoked consideration of DNA as a more dynamic structure. Four-stranded G-quadruplex DNA does not use Watson-Crick base pairing and has been subject of considerable speculation and investigation during the past decade, particularly with regard to its potential relevance to genome integrity and gene expression. Here, we discuss recent data that collectively support the formation of G-quadruplexes in genomic DNA and the consequences of formation of this structural motif in biological processes.
Quadruplex DNA: sequence, topology and structure
Nucleic Acids Research, 2006
G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential quadruplex sequences have been identified in G-rich eukaryotic telomeres, and more recently in non-telomeric genomic DNA, e.g. in nuclease-hypersensitive promoter regions. The natural role and biological validation of these structures is starting to be explored, and there is particular interest in them as targets for therapeutic intervention. This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence. Emphasis is placed on information from the high-resolution methods of X-ray crystallography and NMR, and their scope and current limitations are discussed. Such information, together with biological insights, will be important for the discovery of drugs targeting quadruplexes from particular genes.
Structural Diversity and Specific Recognition of Four Stranded G-Quadruplex DNA
Current Molecular Medicine, 2011
Structural multitude of nucleic acids serves basis for its multiple merits and applications. During structural transitions, significant to perform respective cellular functions, these DNA forms can vary from the single stranded to multi-stranded species. Hence, beyond the image of a monotonous DNA double-helix, there is now increasing interest in other polymorphic/ multi-stranded forms, the roles they may play in vivo and their potential use in therapeutics. Distinct guanine-rich nucleic acid sequences readily form a structurally diverse four-stranded architecture called G-quadruplexes. In addition to their presence at physical ends of chromosomes called telomeres, occurrence of these structural motifs in the upstream promoter regions of a number of genes, oncogenes and near transcription start sites, highlights that G-quadruplexes are involved in regulation of gene expression. Cancer cells typically possess shorter telomeres and have telomerase activity greatly exceeding that of normal cells. These differences create an opportunity to use anticancer therapies targeting telomerase and telomeres. The ability of small molecules to interact with and presumably stabilize Gquadruplex structures as a means of inhibiting telomerase has been a major drug design effort. Ligands, capable of interacting with four-stranded G-quadruplex have been generated. The discovery of proteins including transcription factors, recognizing G-quadruplexes, and conferring stabilization or unfolding them in biological systems, again makes G-quadruplexes, biologically pertinent structures. This review is an attempt to summarize the rapidly evolving literature exploring the amazing polymorphism of G-quadruplexes, and understanding their structure-specific-recognition and biological relevance, keeping in mind that G-tetraplexes are not only important drug targets, but may also act as gene regulatory elements. A pertinent detail of the challenges towards the rational design of structure-specific novel drugs has also been discussed.
Molecular models for intrastrand DNA G-quadruplexes
BMC Structural Biology, 2009
Background: Independent surveys of human gene promoter regions have demonstrated an overrepresentation of G 3 X n1 G3X n2 G 3 X n3 G 3 motifs which are known to be capable of forming intrastrand quadruple helix structures. In spite of the widely recognized importance of Gquadruplex structures in gene regulation and growing interest around this unusual DNA structure, there are at present only few such structures available in the Nucleic Acid Database. In the present work we generate by molecular modeling feasible G-quadruplex structures which may be useful for interpretation of experimental data.
PLOS ONE, 2016
The G-quadruplex is a non-canonical DNA structure biologically significant in DNA replication, transcription and telomere stability. To date, only G4s with all guanines originating from the same strand of DNA have been considered in the context of the human nuclear genome. Here, I discuss interstrand topological configurations of G-quadruplex DNA, consisting of guanines from both strands of genomic DNA; an algorithm is presented for predicting such structures. I have identified over 550,000 non-overlapping interstrand Gquadruplex forming sequences in the human genome-significantly more than intrastrand configurations. Functional analysis of interstrand G-quadruplex sites shows strong association with transcription initiation, the results are consistent with the XPB and XPD transcriptional helicases binding only to G-quadruplex DNA with interstrand topology. Interstrand quadruplexes are also enriched in origin of replication sites. Several topology classes of interstrand quadruplex-forming sequences are possible, and different topologies are enriched in different types of structural elements. The list of interstrand quadruplex forming sequences, and the computer program used for their prediction are available at the web address http://moment.utmb.edu/allquads.
Methods, 2014
In this review, we introduce the biophysical and biochemical methods currently used to investigate the structures and stabilities of tetramolecular DNA G-quadruplexes containing chemical modifications. We hope this paper will guide others as they perform similar experiments leading to more information about the effects of chemical modifications on G-quadruplex formation. The structures of tetramolecular quadruplexes and some higher order structures based on tetramolecular quadruplexes are also described.
2016
All guanine-rich DNA and RNA molecules tend to fold into inter-and intra-molecular structures called G-quadruplexes. The core of a G-quadruplex is composed of at least two adjacent G-tetrads stabilized by monovalent cations. While it has been suggested that there could potentially be over 375 000 quadruplex forming sequences in the human genome alone, only a small number of three-dimensional G-quadruplex structures are known. More structural data are needed to explain their presence and function in vivo. We offer here a short review of experimental methods commonly used to determine G-quadruplex topologies.