Mechanistically, EGFR promoted nuclear accumulation of both BRCA2 and Rad51, and HR activation by competitively inhibiting the binding of BRCA2 and Rad51 to E3 ubiquitin ligase c-Cbl, thereby reducing cancer cell sensitivity to PARPi following ATM-mediated DNA damage signal transmission from the nucleus to the cytoplasm. The gene discussed is EGFR; the disease is cancer.