Parity-dependent hairpin configurations of repetitive DNA sequence promote slippage associated with DNA expansion

Tze Yun Huang, Chung Ke Chang, Ya Fen Kao, Chih Hao Chin, Cheng Wei Ni, Hao Yi Hsu, Nien Jen Hu, Li Ching Hsieh, Shan Ho Chou, I. Ren Lee, Ming Hon Hou

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Repetitive DNA sequences are ubiquitous in life, and changes in the number of repeats often have various physiological and pathological implications. DNA repeats are capable of interchanging between different noncanonical and canonical conformations in a dynamic fashion, causing configurational slippage that often leads to repeat expansion associated with neurological diseases. In this report, we used single-molecule spectroscopy together with biophysical anal-yses to demonstrate the parity-dependent hairpin structural polymorphism of TGGAA repeat DNA. We found that the DNA adopted two configurations depending on the repeat number parity (even or odd). Transitions between these two configurations were also observed for longer repeats. In addition, the ability to modulate this transition was found to be enhanced by divalent ions. Based on the atomic structure, we propose a local seeding model where the kinked GGA motifs in the stem region of TGGAA repeat DNA act as hot spots to facilitate the transition between the two configurations, which may give rise to disease-associated repeat expansion.

Original languageEnglish
Pages (from-to)9535-9540
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number36
DOIs
Publication statusPublished - 2017 Sep 5

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Keywords

  • DNA slippage
  • DNA tandem repeats
  • Single-molecule spectroscopy
  • X-ray crystallography

ASJC Scopus subject areas

  • General

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