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Publication Abstract from PubMed

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

Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.,Li KS, Jordan D, Lin LY, McCarthy SE, Schneekloth JS Jr, Yatsunyk LA Angew Chem Int Ed Engl. 2023 Jun 26;62(26):e202301666. doi: , 10.1002/anie.202301666. Epub 2023 Apr 25. PMID:36995904^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.