The parallel tetrameric DNA G-quadruplex formed by the two-repeat C9orf72 GGGGCC sequence in solution

The abnormal expansion of G-rich hexanucleotide repeat, GGGGCC (G4C2), in chromosome 9 open reading frame 72 ( C9orf72 ) is known to be the prevailing genetic cause two fatal degenerative neurological diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It well that DNA G4C2 repeat with different lengths can form G-quadruplexes which affect gene transcription related ALS/FTD, therefore it crucial understand G-quadruplex structures. Herein, by utilizing nuclear magnetic resonance (NMR) spectroscopy, we examined structure adopted repeats an inosine substitution at position 4, d (G4C2) 2 –I4. We show –I4 folds into eight-layer parallel tetrameric containing dimeric stacking together through π-π interaction via 5′-to-5′ mode solution. Each unit involves propeller loops composed cytosine bases. This result consistent observation crystal . Our work not only sheds light on structural diversity n but also provides a basis for drug design treatment ALS FTD.