Twisting right to left: A…A mismatch in a CAG trinucleotide repeat overexpansion provokes left-handed Z-DNA conformation.

ABSTRACT: Conformational polymorphism of DNA is a major causative factor behind several incurable trinucleotide repeat expansion disorders that arise from overexpansion of trinucleotide repeats located in coding/non-coding regions of specific genes. Hairpin DNA structures that are formed due to overexpansion of CAG repeat lead to Huntington's disorder and spinocerebellar ataxias. Nonetheless, DNA hairpin stem structure that generally embraces B-form with canonical base pairs is poorly understood in the context of periodic noncanonical A…A mismatch as found in CAG repeat overexpansion. Molecular dynamics simulations on DNA hairpin stems containing A…A mismatches in a CAG repeat overexpansion show that A…A dictates local Z-form irrespective of starting glycosyl conformation, in sharp contrast to canon

SUBMITTER: Khan N 

PROVIDER: S-EPMC4395422 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature