DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways.

摘要: The tumor suppressor protein p53 serves as a critical regulator of G1 cell cycle checkpoint and apoptosis following exposure cells to DNA-damaging agents. mechanism by which agents elevate levels trigger G1/S arrest or death remains be elucidated. In fact, whether damage the DNA template itself participates in transducing signal leading induction has not yet been demonstrated. We exposed human lines containing wild-type alleles several different found that rapidly induce strand breaks, such ionizing radiation, bleomycin, topoisomerase-targeted drugs, triggered elevations. addition, we determined camptothecin-stimulated trapping topoisomerase I-DNA complexes was sufficient levels; rather, replication-associated breaks were required. Furthermore, treatment with antimetabolite N(phosphonoacetyl)-L-aspartate (PALA) did cause rapid increases but resulted delayed temporally correlated appearance breaks. Finally, concluded for initiating p53-dependent transduction after finding introduction nucleases into electroporation stimulated While appeared capable triggering induction, lesions other than not. Exposure normal excision repair-deficient xeroderma pigmentosum low doses UV light, under conditions thymine dimers appear prevented, attributable associated repair. Our data indicate are probably necessary