Rudimentary G-quadruplex-based telomere capping in Saccharomyces cerevisiae

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Telomere capping protects chromosome ends but its mechanisms are not fully understood.
• Telomeres can form G-quadruplex (G4) DNA structures, but their in vivo function is unclear.
• Telomere capping in budding yeast depends on Cdc13 protein and is compromised in cdc13-1 mutants at nonpermissive temperatures.

Purpose of the Study:

• To investigate the role of G-quadruplex (G4) DNA in telomere capping.
• To determine if G4 DNA can functionally substitute for natural telomere capping mechanisms.

Main Methods:

• Utilized G4 DNA-stabilizing treatments in cdc13-1 budding yeast mutants.
• Overexpressed G4 DNA binding proteins, disrupted the G4 DNA helicase Sgs1, and used small molecule G4 DNA ligands.
• Performed in vitro assays to assess the effect of protein-bound G4 DNA on exonuclease activity.

Main Results:

• G4 DNA-stabilizing treatments suppressed telomere capping defects in cdc13-1 mutants.
• In vitro, protein-bound G4 DNA on a 3' overhang inhibited 5'→3' resection by exonuclease I.
• These findings indicate a protective role for G4 DNA at telomeres.

Conclusions:

• G-quadruplex (G4) DNA plays a functional role in telomere protection in vivo, particularly when natural capping is impaired.
• G4 DNA structures can inhibit exonuclease activity, contributing to telomere end maintenance.
• This study provides evidence for the functional significance of telomeric G4 DNA in chromosome end protection.