DNA i-motifs, 50.000 loops with unknown function

When you think about DNA, the first thing that probably comes to mind is the double helix model published by Watson and Crick. However, in the 90s scientists identified a particular conformation in DNA molecules in vitro (in a tube): single chain knot-like loops that they called i-motifs. These structures form because, instead of the typical pairing of cytosine – guanine between the two strands of DNA, the cytosines on one chain bind each other forming a brief section that protrudes from the double helix as a four-stranded structure.

As in the first tests the DNA was isolated from cells, many considered them artefacts. However, since then, they have identified in human and plant cells, which indicates that they are probably commonplace in nature.

Although certain sequences in the DNA appear to be more prone to the occurrence of i-motifs, why do they form or how often they appear was unclear. A team of scientists at the Garvan Institute of Medical Research in Australia has recently reported ¹ the identification of around 50,000 i-motifs in 3 human cell lines, further corroborating their existence in biological conditions and indicating that they are indeed a very common structure in DNA.

Further, Cristian David Peña Martinez and colleagues noticed that i-motifs tend to occur more often in DNA regions containing genes highly active at certain times of the cell cycle, indicating that they probably play a regulatory role in gene expression. A supposition supported by their occurrence close to the promoter of the MYC gene, an oncogene –involved in cancer–.

Despite the preliminary nature of the results, if a regulatory role were found for i-motifs in cancer or other diseases, it may become a potential treatment target. However, caution is needed as given how commonplace they are, “touching” them may have unwelcome systemic consequences, like adverse side-effects.