Recently discovered transcription-independent features of p53 involve the choice of DNA damage repair pathway after PARylation, and p53's complex formation with phosphoinositide lipids, PI(4,5)P2 . PARylation-mediated rapid accumulation of p53 at DNA damage sites is linked to the recruitment of downstream repair factors and tumor suppression. This links p53's capability to sense damaged DNA in vitro and its relevant functions in cells. Further, PI(4,5)P2 rapidly accumulates at damage sites like p53 and complexes with p53, while it is required for ATR recruitment. These findings help explain how p53 and PI(4,5)P2 maintain genome stability by directing DNA repair pathway choice. Additionally, there is a strong correlation between p53 sequence homology, genome mutation rates as well as lifespans across various mammalian species. Further investigation is required to better understand the connections between genome stability, tumor suppression, longevity and the transcriptional-independent function of p53.
Keywords: DNA repair pathway selection; PARylation; evolutionary biology; life span; mutation burden; p53; synthetic lethality.
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