Abstract
As if twisting itself into double helices weren’t hard enough, DNA also can fold into structures such as G-quadruplexes and i-motifs, which interrupt normal DNA base pairing. Researchers identified both forms of folded DNA in cell-free systems and showed that they regulate gene transcription, making them potential cancer drug targets. But many questioned whether the folded structures actually existed in the human genome. Scientists found earlier that G-quadruplexes were present in human cells (Nat. Chem. 2013, DOI: 10.1038/nchem.1548 and C&EN, Jan. 21, 2013, page 8). Now a separate group, led by Marcel E. Dinger and Daniel Christ of Garvan Institute of Medical Research, reports that i-motifs exist in human cells too (Nat. Chem. 2018, DOI: 10.1038/s41557-018-0046-3). The work could help lead to i-motif-targeted drugs. I-motifs form when sets of cytosines pair with protonated cytosines, connecting U-shaped DNA strands. Because cytosines are normally protonated under acidic conditions that aren’t present in
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