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Evaluation of the Stability of DNA i‐Motifs in the Nuclei of Living Mammalian Cells
Author(s) -
Dzatko Simon,
Krafcikova Michaela,
HänselHertsch Robert,
Fessl Tomas,
Fiala Radovan,
Loja Tomas,
Krafcik Daniel,
Mergny JeanLouis,
FoldynovaTrantirkova Silvie,
Trantirek Lukas
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201712284
Subject(s) - dna , motif (music) , sequence motif , structural motif , in vitro , in vivo , chemistry , microbiology and biotechnology , biology , computational biology , genome , human genome , dna sequencing , gene , biophysics , genetics , biochemistry , physics , acoustics
C‐rich DNA has the capacity to form a tetra‐stranded structure known as an i‐motif. The i‐motifs within genomic DNA have been proposed to contribute to the regulation of DNA transcription. However, direct experimental evidence for the existence of these structures in vivo has been missing. Whether i‐motif structures form in complex environment of living cells is not currently known. Herein, using state‐of‐the‐art in‐cell NMR spectroscopy, we evaluate the stabilities of i‐motif structures in the complex cellular environment. We show that i‐motifs formed from naturally occurring C‐rich sequences in the human genome are stable and persist in the nuclei of living human cells. Our data show that i‐motif stabilities in vivo are generally distinct from those in vitro. Our results are the first to interlink the stability of DNA i‐motifs in vitro with their stability in vivo and provide essential information for the design and development of i‐motif‐based DNA biosensors for intracellular applications.