G-Quadruplexes Formation by the C9orf72 Nucleotide Repeat Expansion d(GGGGCC)_n and Conformation Regulation by Fangchinoline.

ABSTRACT: The G-quadruplex (GQ)-forming hexanucleotide repeat expansion (HRE) in the C9orf72 (C9) gene has been found to be the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (collectively, C9ALS/FTD), implying the great significance of modulating C9-HRE GQ structures in C9ALS/FTD therapeutic treatment strategies. In this study, we investigated the GQ structures formed by varied lengths of C9-HRE DNA sequences d(GGGGCC)₄ (C9-24mer) and d(GGGGCC)₈ (C9-48mer), and found that the C9-24mer forms anti-parallel GQ (AP-GQ) in the presence of potassium ions, while the long C9-48mer bearing eight guanine tracts forms unstacked tandem GQ consisting of two C9-24mer unimolecular AP-GQs. Moreover, the natural small molecule Fangchinoline wa

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC10300829 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature