p53 Tumor Suppressor Pathway

真核生物基因组不断面临着外源和内源诱变剂的破坏威胁。因此，哺乳动物细胞已经进化出一个复杂的防御网络来维持基因组的稳定性。p53处于这些防御途径的十字路口。我们研究罕见的基因组不稳定性和/或过早衰老疾病，例如，Bloom，Werner，Rothmund-Thomson和Li-Fraumeni Syndrome，以深入了解p53在普通人群中的功能。例如，在DNA复制应激期间，p53与Bloom综合征解旋酶、BLM和前重组原Rad 51合作，充当DNA重组的分子调控者。我们还发现了p53的转录辅因子，即，ING 2 -5，其增强p53效应子在细胞周期检查点、凋亡和衰老中的功能。我们计划继续研究p53介导的复制性衰老的ING家族蛋白或POT 1和WRN，管理端粒磨损调制。

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.