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Related Experiment Video

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Author Spotlight: Characterizing DNA G-Quadruplex by Bis-3-Chloropiperidine Based Chemical Mapping
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A Minimal Sequence for Left-Handed G-Quadruplex Formation.

Blaž Bakalar1,2, Brahim Heddi1,3, Emmanuelle Schmitt4

  • 1School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.

Angewandte Chemie (International Ed. in English)
|November 28, 2018
PubMed
Summary

Scientists discovered the first left-handed DNA G-quadruplex (Z-G4) from natural sources. A minimal 12-nucleotide sequence (GTGGTGGTGGTG) forms this structure, which is common in the human genome.

Keywords:
DNADNA structuresG-quadruplexesX-ray diffractioncircular dichroism

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Genomics

Background:

  • The discovery of DNA G-quadruplexes has expanded our understanding of nucleic acid structures beyond the canonical double helix.
  • While most known G-quadruplexes adopt right-handed helical conformations, the existence and structural basis of left-handed variants in natural DNA remained elusive.

Purpose of the Study:

  • To characterize the first observed left-handed DNA G-quadruplex structure, termed Z-G4, formed from a natural DNA sequence.
  • To identify the minimal sequence motif responsible for the unique left-handed helical twist in Z-G4.
  • To investigate the sequence tolerance of this motif for left-handed G-quadruplex formation.

Main Methods:

  • Circular dichroism (CD) spectroscopy to analyze secondary structure.
  • Nuclear Magnetic Resonance (NMR) spectroscopy for detailed structural insights.
  • X-ray crystallography for high-resolution structural determination.
  • Systematic analysis of sequence variations, specifically thymine loop mutations.

Main Results:

  • The first natural left-handed DNA G-quadruplex (Z-G4) structure was identified and characterized.
  • A minimal 12-nucleotide sequence motif, (GTG)4, was determined to be essential for forming the left-handed Z-G4 structure.
  • This (GTG)4 motif is highly abundant in the human genome.
  • Moderate sequence tolerance was observed in the loops, suggesting a broader range of sequences can form left-handed G-quadruplexes.

Conclusions:

  • The discovery of Z-G4 provides a new class of DNA structures with potential biological significance.
  • The identified (GTG)4 motif offers a specific target for understanding and potentially manipulating left-handed G-quadruplex formation in the human genome.
  • The sequence tolerance indicates that left-handed G-quadruplexes may be more prevalent and functionally relevant than previously thought.