Long-Range Hairpin Slippage Reconfiguration Dynamics in Trinucleotide Repeat Sequences

Cheng Wei Ni, Yu Jie Wei, Yang I. Shen, I. Ren Lee

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Trinucleotide repeat (TNR) sequences, which are responsible for several neurodegenerative genetic diseases, fold into hairpins that interfere with the protein machinery in replication or repair, thus leading to dynamic mutation -abnormal expansions of the genome. Despite their high thermodynamic stability, these hairpins can undergo configurational rearrangements, which may be crucial for continuous dynamic mutation. Here, we used CTG repeats as a model system to study their structural dynamics at the single-molecule level. A unique dynamic two-state configuration interchange was discovered over a wide range of odd-numbered CTG repeat sequences. Employing repeat-number-dependent kinetic analysis, we proposed a bulge translocation model, which is driven by the local instability and can be extended reasonably to longer (pathologically relevant) hairpins, implying the potential role in error accumulation in repeat expansion.

Original languageEnglish
Pages (from-to)3985-3990
Number of pages6
JournalJournal of Physical Chemistry Letters
Volume10
Issue number14
DOIs
Publication statusPublished - 2019 Jun 26

ASJC Scopus subject areas

  • Materials Science(all)
  • Physical and Theoretical Chemistry

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