p53 Tumor Suppressor Pathway

真核生物基因组不断面临外源性和内源性诱变剂损伤的威胁。因此，哺乳动物细胞进化出了一个复杂的防御网络来维持基因组的稳定性。P53位于这些防御途径的十字路口。我们研究了罕见的基因组不稳定和/或早衰疾病，如Bloom、Werner、rothmond - thomson和Li-Fraumeni综合征，以深入了解p53在普通人群中的功能。例如，在DNA复制应激过程中，p53与Bloom综合征解旋酶（BLM）和原重组酶（prorecombinogenic Rad51）合作，作为DNA重组的分子调控因子。我们还发现了p53的转录辅助因子，即ING2-5，可以增强p53在细胞周期检查点、细胞凋亡和衰老中的效应功能。我们计划继续研究由ING家族蛋白或控制端粒磨损的POT1和WRN调节的p53介导的复制性衰老。

The eukaryote genome constantly faces the threat of damage from exogenous and endogenous mutagens. Mammalian cells, therefore, have evolved an intricate network of defenses to maintain genomic stability. p53 is at the crossroads of these defense pathways. We investigate rare genomic instability and/or premature aging diseases, e.g., Bloom, Werner, Rothmund-Thomson, and Li-Fraumeni Syndromes, to gain insight into p53 function in the general population. For example, p53 cooperates with the Bloom Syndrome helicase, BLM, and the prorecombinogenic Rad51 during DNA replicative stress to act as a molecular governor of DNA recombination. We have also discovered transcriptional cofactors of p53, i.e., ING2-5, that enhance p53 effector functions in cell cycle checkpoints, apoptosis, and senescence. We plan to continue studying p53-mediated replicative senescence modulated by either ING family proteins or by POT1 and WRN that govern telomere attrition.