Proceedings of the National Academy of Sciences · 1999 · 573 citations · 32 references
Life SciencesGeneticsMolecular BiologyDna RepairGene ExpressionMolecular OncologyDna DamageDna Double-strand Break RepairDna Repair DefectsDouble-strand Break RepairNucleotide Excision RepairUltraviolet Radiation BiologyDna Damage Repair PathwaysDna Repair MechanismsRepair Of Uv-induced Dna DamageTumor Suppressor P53Tumor Suppressor PathwaysUltraviolet Radiation DamageUltraviolet-induced Dna DamageXeroderma Pigmentosum
Global genomic repair of UV‑induced DNA damage requires p53, yet the underlying mechanism was unclear, and the p48 gene—essential for UV‑damaged DNA binding activity—is disrupted in XP‑E cells lacking this activity. The study shows that p48 transcription is p53‑dependent and upregulated after DNA damage, and that XP‑E cells lacking p48 are deficient in global genomic repair, establishing p48 as the mediator between p53 and the nucleotide excision repair machinery.
In human cells, efficient global genomic repair of DNA damage induced by ultraviolet radiation requires the p53 tumor suppressor, but the mechanism has been unclear. The p48 gene is required for expression of an ultraviolet radiation-damaged DNA binding activity and is disrupted by mutations in the subset of xeroderma pigmentosum group E cells that lack this activity. Here, we show that p48 mRNA levels strongly depend on basal p53 expression and increase further after DNA damage in a p53-dependent manner. Furthermore, like p53(-/-) cells, xeroderma pigmentosum group E cells are deficient in global genomic repair. These results identify p48 as the link between p53 and the nucleotide excision repair apparatus.
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