Crystal Structure of an i‐Motif from the HRAS Oncogene Promoter

An i-motif is a non-canonical DNA structure implicated in gene regulation and linked to cancers. The C-rich strand of the HRAS oncogene, 5′-CGCCCGTGCCCTGCGCCCGCAACCCGA-3′ (herein referred as iHRAS), forms an vitro but its exact was unknown. member RAS proto-oncogene family. About 19 % US cancer patients carry mutations genes. We solved iHRAS at 1.77 Å resolution. reveals that folds into double hairpin. two hairpins associate antiparallel fashion, forming dimer capped by loops on each end connecting region. Six C−C+ base pairs form core, core regions are extended G−G pair cytosine stacking. Extensive canonical pairing stacking stabilizes region loops. first atomic resolution from human oncogene. This sheds light i-motifs folding function cell.