Genomic instability, a hallmark of cancer, is a direct consequence of the inactivation of the tumor suppressor protein p53. Genetically modified mouse models and human tumor samples have revealed that p53 loss results in extensive chromosomal abnormalities, from copy number alterations to structural rearrangements. In this perspective article we explore the multifaceted relationship between p53, genomic stability, and epigenetic control, highlighting its significance in cancer biology. p53 emerges as a critical regulator of DNA repair mechanisms, influencing key components of repair pathways and directly participating in DNA repair processes. p53 role in genomic integrity however extends beyond its canonical functions. p53 influences also epigenetic landscape, where it modulates DNA methylation and histone modifications. This epigenetic control impacts the expression of genes involved in tumor suppression and oncogenesis. Notably, p53 ability to ensure cellular response to DNA demethylation contributes to the maintenance of genomic stability by preventing unscheduled transcription of repetitive non-coding genomic regions. This latter indicates a causative relationship between the control of epigenetic stability and the maintenance of genomic integrity in p53-mediated tumor suppression. Understanding these mechanisms offers promising avenues for innovative therapeutic strategies targeting epigenetic dysregulation in cancer and emphasizes the need for further research to unravel the complexities of this relationship. Ultimately, these insights hold the potential to transform cancer treatment and prevention strategies.

基因组不稳定是癌症的一个标志，是肿瘤抑制蛋白 p53 失活的直接后果。转基因小鼠模型和人类肿瘤样本表明，p53 缺失会导致广泛的染色体异常，从拷贝数改变到结构重排。在这篇前瞻性文章中，我们探讨了 p53、基因组稳定性和表观遗传控制之间的多方面关系，强调了其在癌症生物学中的重要性。p53 成为 DNA 修复机制的关键调节因子，影响修复途径的关键组成部分并直接参与 DNA 修复过程。然而，p53 在基因组完整性中的作用超出了其典型功能。p53 还影响表观遗传景观，调节 DNA 甲基化和组蛋白修饰。这种表观遗传控制影响参与肿瘤抑制和肿瘤发生的基因的表达。值得注意的是，p53 确保细胞对 DNA 去甲基化作出反应的能力，有助于通过防止重复非编码基因组区域的计划外转录来维持基因组稳定性。后者表明在 p53 介导的肿瘤抑制中表观遗传稳定性的控制与基因组完整性的维持之间存在因果关系。了解这些机制为针对癌症表观遗传失调的创新治疗策略提供了有希望的途径，并强调需要进一步研究来阐明这种关系的复杂性。最终，这些见解有可能改变癌症治疗和预防策略。