Long-Range Hairpin Slippage Reconfiguration Dynamics in Trinucleotide Repeat Sequences

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

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

4 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)3985-3990
頁數6
期刊Journal of Physical Chemistry Letters
10
發行號14
DOIs
出版狀態已發佈 - 2019 6月 26

ASJC Scopus subject areas

  • 材料科學(全部)
  • 物理與理論化學

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