4.5 Article

Rudimentary G-quadruplex-based telomere capping in Saccharomyces cerevisiae

Journal

NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 18, Issue 4, Pages 478-U119

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2033

Keywords

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Funding

  1. US National Institutes of Health [R01 AG021521, P01 AG031862, T32 GM008216-22, T32 GM07229]
  2. Camille and Henry Dreyfus Faculty Startup Award
  3. Research Corporation Award [7843]
  4. Deutscher Akademischer Austausch Dienst
  5. Cancer Research UK

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Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3' overhang inhibits 5'-> 3' resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo.

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