Polarizable Molecular Dynamics Simulations of Two c-kit Oncogene Promoter G-Quadruplexes: Effect of Primary and Secondary Structure on Loop and Ion Sampling.

ABSTRACT: G-quadruplexes (GQs) are highly ordered nucleic acid structures that play fundamental roles in regulating gene expression and maintaining genomic stability. GQs are topologically diverse and enriched in promoter sequences of growth regulatory genes and proto-oncogenes, suggesting that they may serve as attractive targets for drug design at the level of transcription rather than inhibiting the activity of the protein products of these genes. The c-kit promoter contains three adjacent GQ-forming sequences that have proposed antagonistic effects on gene expression and thus are promising drug targets for diseases such as gastrointestinal stromal tumors, mast cell disease, and leukemia. Because GQ stability is influenced by primary structure, secondary structure, and ion interactions, a

SUBMITTER: Salsbury AM 

PROVIDER: S-EPMC7221321 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature