Atypical structures of GAA/TTC trinucleotide repeats underlying Friedreich's ataxia: DNA triplexes and RNA/DNA hybrids.

ABSTRACT: Expansion of the GAA/TTC repeats in the first intron of the FXN gene causes Friedreich's ataxia. Non-canonical structures are linked to this expansion. DNA triplexes and R-loops are believed to arrest transcription, which results in frataxin deficiency and eventual neurodegeneration. We present a systematic in silico characterization of the possible DNA triplexes that could be assembled with GAA and TTC strands; the two hybrid duplexes [r(GAA):d(TTC) and d(GAA):r(UUC)] in an R-loop; and three hybrid triplexes that could form during bidirectional transcription when the non-template DNA strand bonds with the hybrid duplex (collapsed R-loops, where the two DNA strands remain antiparallel). For both Y·R:Y and R·R:Y DNA triplexes, the parallel third strand orientation is more stable; both paral

SUBMITTER: Zhang J 

PROVIDER: S-EPMC7515735 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature