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Discuss the role of p53 as guardian of genome 4 marks Question writing guide for university exam abvmu

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p53 guardian of genome DNA damage cell cycle arrest apoptosis NIH

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p53 as the “Guardian of the Genome”

p53 is a tumour-suppressor protein encoded by the TP53 gene. It is called the guardian of the genome because it prevents replication and transmission of damaged DNA to daughter cells.
Role:
  1. Senses cellular DNA damage
    DNA damage, hypoxia, or abnormal oncogene activation activates p53. Normally, p53 is rapidly degraded by MDM2, but after cellular stress it becomes stabilized and active.
  2. Causes cell-cycle arrest
    p53 induces p21, a cyclin-dependent kinase inhibitor. This blocks the G1-to-S phase transition, allowing time for DNA repair before DNA replication.
  3. Promotes DNA repair
    During cell-cycle arrest, p53 activates transcription of genes involved in DNA repair. Thus, cells with repairable damage can survive with an intact genome.
  4. Eliminates irreparably damaged cells
    If damage is severe or cannot be repaired, p53 induces:
    • Apoptosis by increasing pro-apoptotic proteins such as BAX
    • Cellular senescence, producing permanent growth arrest
  5. Prevents cancer formation
    By stopping proliferation of genetically damaged cells, p53 prevents accumulation of mutations and neoplastic transformation. Mutation of TP53 is common in human cancers.
Conclusion:
p53 maintains genomic stability by arresting the cell cycle, facilitating DNA repair, and causing apoptosis or senescence of cells with irreparable DNA damage. Hence it is called the guardian of the genome.
Reference: Robbins & Kumar Basic Pathology, section “TP53: Guardian of the Genome,” lines 3668-3676.
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