p53调控细胞代谢应激从而在肿瘤发生发展中起着关键作用，但机制有待阐明。我们的前期工作发现，dNTP失衡状态下p21介导同源重组修复关键蛋白CtIP降解，进而影响DSB末端切除效率。进一步研究提示p53/p73可能是细胞dNTP水平的感应分子：dNTP失衡会导致p53核内富集，转录激活下游靶分子p21；而在p53突变或缺失型细胞中，dNTP失衡介导的p21转录激活依赖于p73。本课题将围绕p53/p73感受细胞dNTP水平的分子机制及其在肿瘤发生发展中的作用进行深入系统的研究，旨在阐明p53/p73感受dNTP水平的分子机制，增进我们对细胞应激状态下p53/p73功能的认识，为肿瘤的靶向治疗提供新思路。

As a tumor suppressor, p53 plays an important role in the control of metabolic balance. When the cells are response to different physiological stresses, the activated p53 will affect various metabolic pathways by participating in the regulations of glucose metabolism, fatty acid metabolism, ROS level, etc. We have previously identified p53/p73-dependent transcriptional activation of p21 as the important molecular link between dNTP pool deprivation and declined CtIP stability. p21 is transcriptionally activated by p53 or p73 in coping with dNTP pool imbalance, and that p73 functions as a p53 counterpart in p53-inactivated cells. Interestingly, the activation of p53/p73 is correlated with increased nuclear entry and chromatin recruitment to p21 promoter region. Together, these data suggest p53/p73 function as sensors of the dNTP pool to cope with nucleotide metabolism disorders. This project focuses on the function role and mechanism of p53/p73 sensing dNTP, to provide mechanistic insights into the cellular dNTP pool sensing pathway, advance our understanding of p53/p73 in metabolic regulation under physiological stresses, and identify potential therapeutic strategies.