Abstract
Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc.), the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Sequences with the potential to form quadruplexes are widely present in genome of all organisms. They are found often in repetitive sequences such as telomeric ones, and also in promoter regions and 5' non-coding sequences. Recently, many proteins with binding affinity to G-quadruplexes have been identified. One of the initially portrayed G-rich regions, the human telomeric sequence (TTAGGG)n, is recognized by many proteins which can modulate telomerase activity. Sequences with the potential to form G-quadruplexes are often located in promoter regions of various oncogenes. The NHE III1 region of the c-MYC promoter has been shown to interact with nucleolin protein as well as other G-quadruplex-binding proteins. A number of G-rich sequences are also present in promoter region of estrogen receptor alpha. In addition to DNA quadruplexes, RNA quadruplexes, which are critical in translational regulation, have also been predicted and observed. For example, the RNA quadruplex formation in telomere-repeat-containing RNA is involved in interaction with TRF2 (telomere repeat binding factor 2) and plays key role in telomere regulation. All these fundamental examples suggest the importance of quadruplex structures in cell processes and their understanding may provide better insight into aging and disease development.
Highlights
The discovery of the B-DNA structure was one of the most important events in natural science during the last century [1]
BRCA1, breast cancer type 1 susceptibility protein; hnRNP, heterogeneous nuclear ribonucleoprotein; POT1, protection of telomeres 1; RPA, replication protein A; telomere end binding protein (TEBP), Telomere End Binding Protein; TLS/FUS, translocated in liposarcoma/fused in sarcoma; Topo I, Topoisomerase I; TRF2, telomere repeat binding factor 2; UP1, unwinding protein 1; PARP-1, Poly [ADP-ribose] polymerase 1; CNBP, cellular nucleic-acid-binding protein; IGF-2, Insulin-like growth factor 2; MAZ, myc-associated zinc-finger; FMR2, fragile X mental retardation 2; RHAU, the RNA helicase associated with AU-rich element; SRSF, serin/arginine-rich splicing factor; BLM, Bloom syndrome protein; Dna2, DNA replication helicase/nuclease 2; G4R1, G4 Resolvase 1; FANCJ, Fanconi anemia complementation group J; Sgs1, small growth suppressor 1; WRN, Werner syndrome ATP-dependent helicase
FMR2 is able to bind the G-quartet-forming RNA structure with high affinity [66]. These findings suggest that FMR2 is an RNA-binding protein, which could be involved in alternative splicing regulation through interaction with the RNA quadruplex structure
Summary
The discovery of the B-DNA structure was one of the most important events in natural science during the last century [1]. Knowledge of the DNA sequences and structures has led to fascinating findings of various DNA forms that differ from the canonical right-handed Watson–Crick double–helix. These unusual DNA structures play critical roles in regulation of very basic biological functions and are integral part of the complex regulatory systems of living beings. The negative supercoiling of DNA can induce sequence-dependent conformational changes that give rise to local. DNA structures and alternative DNA conformations such as cruciforms, A-DNA, left-handed DNA (Z-DNA), triplexes, four-stranded DNA (quadruplexes) and others [2,3]
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