Slow motions in A·T rich DNA sequence
A Ben Imeddourene1, L Zargarian1, M Buckle1
1LBPA, ENS de Paris-Saclay, UMR 8113 CNRS, Institut D'Alembert, Université Paris-Saclay, 4, avenue des Sciences, 91190, Gif-sur-Yvette, France.
Scientific Reports
|November 5, 2020
Summary
DNA exhibits slow conformational exchanges between Watson-Crick and Hoogsteen base-pairing, particularly in TAA segments. These dynamics, observed using NMR, reveal transient Hoogsteen pairs that influence DNA structure and protein interactions.
Area of Science:
- Molecular Biology
- Biophysics
- Structural Biology
Background:
- Free B-DNA exhibits dynamic motions beyond standard base-pairing.
- Slow conformational exchanges (microsecond-to-millisecond) can mediate DNA-protein assemblies.
- Watson-Crick (WC) and Hoogsteen (HG) base-pairing represent distinct DNA conformations.
Purpose of the Study:
- To investigate slow conformational dynamics in a DNA dodecamer with a TTAAA element using NMR.
- To identify transient base-pairing conformations and their role in DNA structure.
- To understand how DNA sequence modulates dynamics on the micro- to millisecond timescale.
Main Methods:
- Utilized R1ρ relaxation dispersion NMR spectroscopy.
- Employed 13C/15N labeled DNA for enhanced signal detection.
- Analyzed NMR data to infer exchange parameters and conformational populations.
Main Results:
- Identified transient Hoogsteen (HG) base pairs within the TAA·TTA segment of the DNA dodecamer.
- Observed HG base pairs as minor conformers with an abundance up to 1.2%.
- Demonstrated non-simultaneous motions of adenine bases, optimizing HG pair formation.
Conclusions:
- The TAA·TTA sequence facilitates transient HG base-pairing in DNA.
- DNA sequence plays a crucial role in modulating dynamics across various timescales.
- These findings enhance understanding of DNA functional elements and their dynamic repertoire for protein binding.
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