Genome-wide CRISPR screens identify the EXO1-CAF-1 pathway suppressing R-loop-associated DNA damage - PubMed
4 hours ago
- #CRISPR screens
- #DNA repair
- #Genomic stability
- Genome-wide CRISPR screens identified the EXO1-CAF-1 pathway as a suppressor of R-loop-associated DNA damage.
- EXO1 is a 5'-3' exonuclease with multiple roles in DNA biology, crucial for repairing cisplatin-induced DNA damage.
- CRISPR loss-of-function screens revealed differential regulators of cisplatin sensitivity between wildtype and EXO1-deficient cells.
- DNA repair was the main process suppressing cisplatin sensitivity in wildtype cells, but not in EXO1-deficient cells.
- A synthetic lethality interaction was found between EXO1 and the histone chaperone CAF-1.
- EXO1 and CAF-1 are independently recruited to R-loops and work in synergistic pathways to suppress R-loop accumulation.
- Loss of both EXO1 and CAF-1 leads to R-loop accumulation and increased DNA damage, even without genotoxic treatment.
- The study highlights EXO1's critical role in maintaining genomic stability.