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PARPi and synthetic lethality. Single-strand DNA breaks (SSB) lead to PARP1/2 recruitment and activation; PARPi is retained in DNA and results in replication fork stalling. The resulting double-strand DNA breaks (DSB) require homologous recombination (HR) pathway integrity for repair; thus, HR-deficient (BRCA mutant) cells are unable to DNA repair, resulting in cell death.
