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Seminars

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  • Title:Parity-dependent Hairpin Configurations of Repetitive DNA Sequence Promote Slippage Associated with DNA Expansion
  • Start Date/Time:2018-05-01 / 12:00
  • End Date/Time :2018-05-01 / 13:20
    • Speaker:Prof. I-Ren Lee (NTNU)
    • Place:Lecture Room A of NCTS, 4F, General Building III, NTHU
    • Host:Prof. Lee-Wei Yang (NTHU)
    • Abstract: 
      Repetitive DNA sequences are omnipresent 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 dynamically, causing configurational slippage that often leads to repeat expansion associated with neurological diseases. We used single-molecule spectroscopy to demonstrate the parity-dependent hairpin structural polymorphism of TGGAA and CTG 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, which may give rise to disease-associated repeat expansion. With the repeat-number-dependent kinetic analysis of the single-molecule dynamics, we propose a bulge diffusion model: the configuration interconversion is facilitated by a bulge, formed by the local DNA melting during the loop reconfiguration, diffusing through the stem of the hairpin. This local instability driven mechanism can be extended to a longer hairpin regardless the much higher global stability, perhaps permit the repeat expansion at the pathological-relevant repeat-number range.
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