Structural dynamics of tandem repeats of DNA associated with neurodegenerative diseases

Overexpansion of tandem repeats of DNA often causes neurodegenerative diseases. These tandem repeats usually fold into non-canonical secondary structures such as hairpin, G-quadruplex, and more, which are believed to be one of the key factors to induce the gene expansion during the replication, repair, or recombination processes. Our group focus on the structural dynamics studies of these tandem repeats using single-molecule fluorescence resonance energy transfer (smFRET) microscopy. With the unique capability of smFRET in resolving systems with heterogeneities, we aim to reveal the dynamic behavior of these secondary structures at nanometer spatial resolution. Through systematic size-dependent studies, we are looking for the causes of the error-prone expansion, hence, shed the light on preventing or treating these diseases.

 

Publications

Cheng-Wei Ni, Yu-Jie Wei, Yang-I Shen, and I-Ren Lee* "Long-Range Hairpin Slippage Reconfiguration Dynamics in Trinucleotide Repeat Sequences" J. Phys. Chem. Lett. 2019, 10(14): 3985-3990.

| Pubmed | ACS | PDF | Journal of Physical Chemistry Letters Spotlights

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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*, and Ming-Hon Hou* "Parity-dependent hairpin configurations of repetitive DNA sequence promote slippage associated with DNA expansion" Proc Natl Acad Sci U S A. 2017, 114(36): 9535–9540 | Pubmed | PNAS | PDF