SURVEY AND SUMMARY Quadruplex DNA: sequence, topology and structure

SURVEY AND SUMMARY Quadruplex DNA: sequence, topology and structure

2006, Vol. 34, No. 19 | Sarah Burge, Gary N. Parkinson, Pascale Hazel, Alan K. Todd and Stephen Neidle*
G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences, characterized by tetrads of hydrogen-bonded guanine bases. These structures have been identified in G-rich eukaryotic telomeres and non-telomeric genomic DNA, such as nuclease-hypersensitive promoter regions. The natural role and biological significance of these structures are being explored, particularly as potential therapeutic targets. This survey focuses on the folding and structural features of quadruplexes formed from telomeric and non-telomeric DNA sequences, examining fundamental aspects of topology and sequence relationships. High-resolution methods like X-ray crystallography and NMR spectroscopy provide detailed insights into the structure and dynamics of quadruplexes, which are crucial for understanding their biological functions and developing drugs targeting specific genes. The review discusses the general features of quadruplex topology and structure, including the formation and stability of G-quadruplexes, methods for determining quadruplex topology and structure, and the diversity of tetramolecular, bimolecular, and unimolecular quadruplex structures. It also highlights the occurrence of potential quadruplex-forming sequences in non-telomeric regions of the human genome, particularly in promoter regions and cancer-related genes. The biological implications of these sequences, including their potential role in gene regulation, are discussed, along with the challenges in predicting and characterizing quadruplex structures in vivo.G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences, characterized by tetrads of hydrogen-bonded guanine bases. These structures have been identified in G-rich eukaryotic telomeres and non-telomeric genomic DNA, such as nuclease-hypersensitive promoter regions. The natural role and biological significance of these structures are being explored, particularly as potential therapeutic targets. This survey focuses on the folding and structural features of quadruplexes formed from telomeric and non-telomeric DNA sequences, examining fundamental aspects of topology and sequence relationships. High-resolution methods like X-ray crystallography and NMR spectroscopy provide detailed insights into the structure and dynamics of quadruplexes, which are crucial for understanding their biological functions and developing drugs targeting specific genes. The review discusses the general features of quadruplex topology and structure, including the formation and stability of G-quadruplexes, methods for determining quadruplex topology and structure, and the diversity of tetramolecular, bimolecular, and unimolecular quadruplex structures. It also highlights the occurrence of potential quadruplex-forming sequences in non-telomeric regions of the human genome, particularly in promoter regions and cancer-related genes. The biological implications of these sequences, including their potential role in gene regulation, are discussed, along with the challenges in predicting and characterizing quadruplex structures in vivo.
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