Biochemistry and Molecular Biology Department University of Texas Medical Branch, Galveston, TX, 77555, United States.
Bioessays. 2023 Jan;45(1):e2200122. doi: 10.1002/bies.202200122. Epub 2022 Nov 20.
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)P . 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)P 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)P 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.
最近发现的 p53 转录独立特征涉及 PARylation 后 DNA 损伤修复途径的选择，以及 p53 与磷酸肌醇脂质 PI(4,5)P 的复杂形成。PARylation 介导的 p53 在 DNA 损伤部位的快速积累与下游修复因子和肿瘤抑制因子的募集有关。这将 p53 在体外检测受损 DNA 的能力与其在细胞中的相关功能联系起来。此外，PI(4,5)P 像 p53 一样迅速在损伤部位积累并与 p53 形成复合物，而 ATR 的募集则需要 PI(4,5)P。这些发现有助于解释 p53 和 PI(4,5)P 如何通过指导 DNA 修复途径选择来维持基因组稳定性。此外，不同哺乳动物物种之间的 p53 序列同源性、基因组突变率和寿命之间存在很强的相关性。需要进一步研究以更好地理解基因组稳定性、肿瘤抑制、长寿和 p53 转录独立功能之间的联系。
