Prime editing allows fast testing and understanding of selective MutSβ blockers

Approximately 72,000 small molecules were screened for their effects on MutSβ-directed DNA mismatch repair.

• DNA mismatch repair (MMR) is crucial for maintaining genome stability but is linked to the expansion of pathogenic repeats in certain disorders.
• A novel noncanonical 'loop-directed' mechanism of MMR was identified through profiling core MMR genes.
• New scalable reporters were developed to detect the loss of specific MMR processes.
• A series of inhibitors targeting MutSβ was discovered, which may reduce (CAG)n expansion in a cell model.
• Multiple methods for systematically studying MMR were established, showing potential for identifying therapeutic inhibitors.

Simplified