A CRISPR-Cas9-based tool for dose-dependent DNA damage detection

FEBS J. 2025 Nov;292(21):5625-5628. doi: 10.1111/febs.70186. Epub 2025 Jul 13.

Abstract

Auboiron et al. developed a CRISPR-Cas9-based system in yeast Saccharomyces cerevisiae that allows precise, dose-dependent induction of DNA double-strand breaks by targeting Ty retrotransposons. This system combines sequence specificity with control over break numbers (×1, ×15, or ×59), enabling a more detailed and precise study of DNA damage response. It revealed that the key DNA damage response kinase, Tel1, localizes to the nuclear periphery and forms multiple foci after induction of DNA double-strand breaks. The system also exposed limitations in Cas9 availability at higher break levels and offers a scalable platform for studying genome stability across organisms.

Keywords: AT; CRISPR‐Cas9; DNA double‐strand breaks; NHEJ; Tel1; homologous recombination.

MeSH terms

  • CRISPR-Cas Systems* / genetics
  • DNA Breaks, Double-Stranded*
  • DNA Damage* / genetics
  • Intracellular Signaling Peptides and Proteins
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Retroelements / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae* / genetics

Substances

  • Protein Serine-Threonine Kinases
  • Retroelements
  • Saccharomyces cerevisiae Proteins
  • TEL1 protein, S cerevisiae
  • Intracellular Signaling Peptides and Proteins