Dependencies of DNA damage response genes to different types and qualities of ionizing radiation

Kurzfassung

Background Radiation quality influences DNA damage complexity and repair. Particle irradiation is used in clinical treatment for its enhanced precision; particularly, high-LET ions such as carbon ions are postulated to overcome resistance by inducing complex, non-repairable DNA damage. Differences in radiosensitivity linked to DNA repair gene loss have recently gained interest One option to exploit such vulnerabilities is synthetic lethality. However, a systematic approach for exploring synthetically lethal gene defects across distinct beam qualities is currently missing. This study is the first to employ a CRISPR-Cas9 screen and analysis of DNA repair kinetics to systematically investigate the interplay between radiation type, dose, and DNA repair processes, laying the foundation for precision therapeutic interventions.