Year 2

The goal of this proposal is to investigate the mechanisms that maintain the genomic stability of human ES cells (hESCs). We are focusing on the tumor suppression pathways ATM and p53, which are well established guardians of the genome in differentiated cells. In addition, we are investigating the pathways that govern the self-renewal of hESCs, which might be coordinated with DNA damage responses to maintain the genomic stability in hESCs. During the reporting period, we made significant progress towards our goals. First, we developed high efficiency homologous recombination technology to successfully disrupted ATM and p53 in hESCs. Analysis of the mutant ES cells indicate the roles of ATM and p53 in maintaining genomic stability in hESCs. Second, we identified pathways that are important for the self-renewal of hESCs. Third, we employed the knock-in tech