Ontology highlight
ABSTRACT:
SUBMITTER: Haeusler AR
PROVIDER: S-EPMC4046618 | biostudies-literature | 2014 Mar
REPOSITORIES: biostudies-literature
Haeusler Aaron R AR Donnelly Christopher J CJ Periz Goran G Simko Eric A J EA Shaw Patrick G PG Kim Min-Sik MS Maragakis Nicholas J NJ Troncoso Juan C JC Pandey Akhilesh A Sattler Rita R Rothstein Jeffrey D JD Wang Jiou J
Nature 20140305 7491
A hexanucleotide repeat expansion (HRE), (GGGGCC)n, in C9orf72 is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we identify a molecular mechanism by which structural polymorphism of the HRE leads to ALS/FTD pathology and defects. The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA•DNA hybrids (R-loops). The structural polymorphism causes a repeat-length-dependent accumulat ...[more]