Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alt...

We now present the first example in which triplet repeat DNAs adopt the i-motif structure at neutral pH by molecular crowding. Crowding stabilized the i-motif and the pK(a) of N3 of cytosine was raised in such a microenvironment. Molecular crowding is known to accelerate the formation of the multi-stranded i-motif while the triplet repeats adopt the single-strand structure.

BACKGROUND Over 15 inherited diseases are caused by expansion of triplet-repeats. Friedreich ataxia (FRDA) patients are homozygous for an expanded GAA triplet-repeat sequence in intron 1 of the FXN gene. The expanded GAA triplet-repeat results in deficiency of FXN gene transcription, which is reversed via administration of histone deacetylase inhibitors indicating that transcriptional silencing...

BACKGROUND The trinucleotide repeats AAT•ATT are simple DNA sequences that potentially form different types of non-B DNA secondary structures and cause genomic instabilities in vivo. METHODOLOGY AND PRINCIPAL FINDINGS The molecular mechanism underlying the maintenance of a 24-triplet AAT•ATT repeat was examined in E. coli by cloning the repeats into the EcoRI site in plasmid pUC18 and into th...

The abnormal number of repeats found in triplet repeat diseases arises from 'repeat instability', in which the repetitive section of DNA is subject to a change in copy number. Recent studies implicate transcription in a mechanism for repeat instability proposed to involve RNA polymerase II (RNAPII) arrest caused by a CTG slip-out, triggering transcription-coupled repair (TCR), futile cycles of ...