Structural Dynamics Role of AGG Interruptions in Inhibition CGG Repeat Expansion Associated with Fragile X Syndrome

Yang I. Shen, Kai Chun Cheng, Yu Jie Wei, 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

摘要

Abnormal expansion of trinucleotide CGG repeats is responsible for Fragile X syndrome. AGG interruptions in CGG repeat tracts were found in most healthy individuals, suggesting a crucial role in preventing disease-prone repeat expansion. Previous biophysics studies emphasize a difference in the secondary structure affected by AGG interruptions. However, the mechanism of how AGG interruptions impede repeat expansion remains elusive. We utilized single-molecule fluorescence resonance energy transfer spectroscopy to investigate the structural dynamics of CGG repeats and their AGG-interrupted variants. Tandem CGG repeats fold into a stem-loop hairpin structure with the capability to undergo a conformational rearrangement to modulate the length of the overhang. However, this conformational rearrangement is much more retarded when two AGG interruptions are present. Considering the significance of hairpin slippage in repeat expansion, we present a molecular basis suggesting that the internal loop created by two AGG interruptions acts as a barrier, obstructing the hairpin slippage reconfiguration. This impediment potentially plays a crucial role in curbing abnormal expansion, thereby contributing to the genomic stability.

原文英語
頁(從 - 到)230-235
頁數6
期刊ACS Chemical Neuroscience
15
發行號2
DOIs
出版狀態已發佈 - 2024 1月 17

ASJC Scopus subject areas

  • 生物化學
  • 生理學
  • 認知神經科學
  • 細胞生物學

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