Abstract
Although the telomeric sequence has been reported to form various G-quadruplex topologies in vitro and in Xenopus laevis oocytes, in living human cells, the topology of telomeric DNA G-quadruplex remains a challenge. To investigate the human telomeric DNA G-quadruplex in a more realistic human cell environment, in the present study, we demonstrated that the telomeric DNA sequence can form two hybrid-type and two-tetrad antiparallel G-quadruplex structures by in-cell 19F NMR in living human cells (HELA CELLS). This result provides valuable information for understanding the structures of human telomeric DNA in living human cells and for the design of new drugs that target telomeric DNA.
Highlights
Human telomeric DNA exists at the end of chromosome and has important functions in cancer and aging [1,2,3]
We demonstrated for the first time that the telomeric DNA sequence forms the hybrid1, hybrid-2 and two-tetrad antiparallel G-quadruplex structures in living human cells
1D 19F NMR spectroscopy was used as a powerful tool to study telomeric DNA and RNA structures in vitro and in Xenopus laevis oocytes [24,25,26]
Summary
Human telomeric DNA exists at the end of chromosome and has important functions in cancer and aging [1,2,3]. We demonstrated for the first time that the telomeric DNA sequence forms the hybrid1, hybrid-2 and two-tetrad antiparallel G-quadruplex structures in living human cells. One sharp peak at −62.57 ppm was observed, which is consistent with the 1H NMR and CD results and with a previous report that showed the 19F-labeled ODN 1 sequence could form an antiparallel G-quadruplex in Na+ solution (Figure 1B) [12].
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