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Examination of the Telomere G-overhang Structure in Trypanosoma brucei
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Emerging accessibility patterns in long telomeric overhangs.

Sajad Shiekh1, Golam Mustafa1, Sineth G Kodikara1

  • 1Department of Physics, Kent State University, Kent, OH 44242.

Proceedings of the National Academy of Sciences of the United States of America
|July 20, 2022
PubMed
Summary
This summary is machine-generated.

Human telomeric overhangs show periodic accessibility patterns based on length, revealing folding frustration. The junction between single- and double-stranded telomeres is most accessible, crucial for shelterin protein complex assembly.

Keywords:
FRET-PAINTG-quadruplexsingle moleculetelomere

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Area of Science:

  • Molecular Biology
  • Biophysics
  • Genetics

Background:

  • Human telomeres protect chromosome ends and consist of repetitive sequences.
  • Telomeric overhangs can form G-quadruplex (GQ) structures, influencing telomere function.
  • The accessibility of these overhangs is critical for telomere maintenance and protection by shelterin proteins.

Purpose of the Study:

  • To investigate the accessibility of human telomeric overhangs with varying lengths and GQ structures.
  • To understand how overhang length and folding landscape influence accessibility patterns.
  • To correlate accessibility with the stability and folding frustration of G-quadruplex structures.

Main Methods:

  • Employed single-molecule FRET-PAINT experiments using a peptide nucleic acid probe.
  • Studied 25 different telomeric overhangs with 4-28 repeats of the GGGTTA sequence.
  • Developed a computational model to analyze folding stabilities and cooperativities of G-quadruplexes.

Main Results:

  • Observed periodic changes in overhang accessibility correlated with the number of G-Tract repeats.
  • [4n]G-Tract overhangs exhibited broader accessibility, while [4n+2]G-Tract overhangs showed narrower accessibility patterns.
  • The junction between single- and double-stranded telomeres was found to be the least stable and most accessible region.

Conclusions:

  • Folding frustration is higher in [4n]G-Tract constructs compared to [4n+2]G-Tract constructs.
  • The telomeric overhang junction is a key accessible site for protein interactions.
  • Findings are significant for understanding the assembly of the POT1/TPP1 and shelterin protein complex at telomeres.