Movie 1. (VIDEO)
Caption
An electron migrates through the DNA and the DNA/RNA hybrid duplex. In this study, the electron loss center (hole) moved through the duplex; and the movie represents the movement of the hole (white sphere). Because the electron transfer rate depends on the nucleic acid sequence, one can read the sequence information by measuring the electron transfer kinetics. In this study, we focused on detecting the R132H c.395 G>A mutation, a point mutation in IDH1 mRNA that is common in adult grade II and III gliomas. DNA probes designed to hybridize with IDH1 mRNA in cells began to blink upon hybridization, which facilitated measurement of the electron transfer kinetics. By measuring the OFF-time during blinking, we accessed the dynamics of electron transfer. In the probe/mutant duplex, blinking occurred faster than in the probe/wild-type duplex. We observed fast blinking in pathological sections of cell blocks that overexpressed IDH1 mutant RNA, whereas we observed little blinking in cell blocks that expressed only wild-type IDH1. This would allow us to identify pathological specimens obtained during surgery, as presented as a future prospect in the last part of this movie. By using the injected hole as a pulse of sound—analogous to the ping of an active sonar system—and measuring the time required for the hole to return, one can read information on the nucleic acid sequence that is associated with the fluorescent molecule.
Credit
2022, Shunya Fan et al. Electron transfer kinetics through nucleic acids untangled by single-molecular fluorescence blinking. Chem.
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License
CC BY