i-motifs: DNA structures with regulatory functions and therapeutic potential

Non-B DNA structures represent alternative conformations to the canonical double helix, characterized by unconventional base pairing that diverge from the Watson-Crick model. Among these, the i-motifs, formed in cytosine-rich regions, has attracted considerable attention due to its potential regulatory roles. This review examines the molecular mechanisms underlying the formation and stability of i-motifs, which rely on hydrogen bonding between protonated cytosines. These structures can form under slightly acidic and even neutral pH conditions, depending on the DNA sequence context. Their diverse topologies and capacity to interact with specific proteins and ligands suggest that i-motifs play important roles in the regulation of gene expression, particularly within promoters of oncogenes, as well as in telomeric and centromeric regions. Understanding the behavior and biological relevance of i-motifs may deepen our insight into genomic regulation and reveal novel therapeutic opportunities. Targeting i-motif structures therefore represents a promising strategy for the treatment of cancer and other complex diseases.