Cellular Responses to DNA Damage

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

We are examining the role of a subset of nuclear membrane proteins in coordinating dynamic changes in nuclear architecture during the cell cycle and in response to DNA damage. We have identified sites of cell cycle-dependent post-translational modification and are using a variety of functional assays to define the roles these modifications play in response to signals for cell division and DNA damage. In addition, we have developed a CRISPR-cas9-engineered cell reporter system to screen for cell cycle arrest and apoptosis in high-throughput assays of small molecule chemical libraries. We hope this reporter system will yield important new information in early rounds of library screening for apoptotic agents that will facilitate subsequent validation steps. Using genome-wide knockdown screens, we are identifying molecular pathways that are altered or disrupted in response to treatment of cells with selected compounds that induce cell cycle arrest in mitosis and subsequently, cell death.