BRCA proteins prevent the degradation of nascent DNA after replication stress; therefore, nascent DNA generated from stalled forks is degraded by MRE11 nuclease in BRCA-deficient cells, resulting in excessive genomic instability and apoptosis; that is, restoring fork stabilization in BRCA-deficient cells may be responsible for triggering PAPR inhibitor resistance, and a comprehensive understanding of how cells protect stalled forks could lead to the establishment of strategies to combat PARP inhibitor resistance in cancer treatment [55,60,62,63,64]. The gene discussed is PARP1; the disease is cancer.