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This lecture delves into the role of p53 as the 'Master Guardian' in cellular and genetic stability, focusing on its functions in DNA damage response, cell cycle regulation, and apoptosis. The prevalence and impact of TP53 mutations in various tumors are discussed, along with the mechanisms of missense mutations in the DNA-binding domain. The lecture also covers the classification of oncogenes and tumor suppressor genes based on mutation patterns, as well as the repair mechanisms for DNA double-strand breaks. Key concepts include the synthetic lethality concept and the sensitivity of BRCA-deficient cells to PARP inhibitors.