Thermally activated irreversible homogenization of G-quadruplexes in an ALS/FTD-associated gene.

ABSTRACT: A significant proportion of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases exhibit a substantial copy number expansion of the hexanucleotide GGGGCC/GGCCCC sequence in the C9ORF72 gene. The GGGGCC sequence forms a non-canonical DNA structure called a G-quadruplex (G4) which has been associated with the disease states and with nucleic acid condensate formation. G4s can fold into various topologies, which can differentially impact fidelity of DNA synthesis. However, how G4 conformational heterogeneity and its regulation impact hexanucleotide repeat expansion is unclear, and important clues may lie in the thermodynamic properties of different G4 topologies. Here, we use temperature-swept CD spectroscopy to observe configurational homogenization of a

SUBMITTER: Ross D 

PROVIDER: S-EPMC12697674 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature