Investigation on the competition of duplex/ G-quadruplex/ i-motif in telomere sequences and c-MYC gene with a solid-state nanopore sensor

Apart from duplex helix, the coexisted noncanonical DNA may be involved in inhibiting DNA replication, and controlling gene expression. The competition of duplex/ G4/ i-motif depends on many factors, including sequence information, external conditions and binding effects. This work looked into the human telomere sequences of different length (hTelo-1, 2) and intramolecular G-rich and C-rich strands (hTelo-3, 4, 5). Nanopore translocation properties suggested that in the presence of their complementary sequences in the mixed K + /Cs + buffer, G4 was the major species, and G4 from hTelo-2 that holds multiple G-quartets formed slower than shorter hTelo-1. The intramolecular G/C-rich strands hTelo-3, 4, 5 predominantly formed duplex rather than quadruplex under K + or acidic conditions, indicating that intramolecular quadruplex is less stable than duplex due to the strand strain. Translocation behaviors of mixed proto-oncogene cMYC/c-cMYC illustrated that G4 was formed in both K + and Cs + , and Cs + inhibited the duplex formation in K + /Cs + buffer. The increase of the ratio of Cs + will decrease the duplexes species. Our work demonstrated the relative stability of duplex/quadruplex under various conditions with distinct strands, which is useful for the investigation of DNA secondary structural dynamics and transition mechanism in biological function regions, and paved the way for the potential of disease-targeted diagnosis. Duplex/ quadruplex/ i-motif competition monitored with SSN • Firstly and directly determine the duplex/quadruplex competition via SSN molecular translocation without carrier or marker. • Disclosed the competition process of duplex/quadruplex with inter-/intramolecular hTelo sequences and pro-oncogene cMYC. • Characterized the competition of duplex/quadruplex via S1 nuclease digestion for inter-/intramolecular hTelo and cMYC.