- Sombodhi Bhattacharya
G quadruplexes are non linear DNA structures formed at G rich regions. These are formed where strands of DNA or RNA that contain at least four stretches of two or more adjacent guanine nucleotides, for example G2– 5Xn,G2–5Xn,G2–5Xn,G2–5Xn, where X can be up to seven spacer nucleotides, are able to form structures termed G-quadruplexes. These structures have a cationic centre which bonds with the G residues via Hoogsteen bonds.
These can exist between DNA strands, between a DNA and RNA and in RNA. These structures are mostly found in the telomeric regions of the chromosome as they are rich in Guanine residues.
Telomere length is controlled by the telomerase enzyme. This enzyme can only act on the single stranded telomere and stays silent in complex structures like G quadruplexes, hence reducing the length of the telomeres and making the cell prone to apoptosis. Due to this phenomenon, this is an active area of research in Disease manifestation and therapeutics.
These can be detected in Cells by using G quadruplexes specific antibodies. Recently another flurophore SiR-PyPDS has been discovered which binds to these structures and detects it at a higher efficiency than the antibody method.
Two of the major diseases, where these structures have been detected are Cancer and Neurodegenerative disorders.
G-repeats in the C9orf72 gene lead to the formation of G quadruplexes. G4C2 repeats in C9orf72 lead to formation of DNA-RNA hybrids, known as R-loops, which stall RNA polymerase, leading to lower levels of full-length C9orf72 transcripts and causing accumulation of abortive transcripts containing G-quadruplex structures. This leads to increasing risk of FTD and ALS.
These are also used in Cancer therapy. G quadruplex stabilizing ligands are being developed, which will bind and stabilize these structures. These are injected to cancer cells which stabilizes G quadruplexes, and make them more prone to apoptosis.
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