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Circular dichroism (CD) is remarkably sensitive to the conformational states of nucleic acids; therefore, CD spectroscopy has been used to study most features of DNA and RNA structures. Quadruplexes are among the significant noncanonical nucleic acids architectures that have received special attentions recently. G-quadruplex secondary structures (G4) are formed in nucleic acids by sequences that are rich in guanine. They are helical in shape and contain guanine tetrads that can form from one, two or four strands. Several endogenous proteins have been found to interact with DNA G4s, including helicases, transcription factors, and epigenetic and chromatin remodellers. Detailed structural and functional studies provided novel insight into G4–protein interactions and revealed a potential involvement of G4s in a range of biological processes.