During the reporting period, we have made significant progress toward the following research aims: (1). We further mechanistically characterized how PTM regulates H2A.X (key mediator of DNA repair), and DNA sequence specificity (genome-wide fragile sites). (2). Through SILAC-based chemical proteomics, the interacting proteins of PTM were identified and mechanistically characterized. (3) In human stem cells, PTM mediated homologous recombination to protect cells and enhance genome editing was further characterized.