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-dependent post-translational modification of these proteins 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.

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12
Fiscal Year
2018
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U.S. National Inst Diabetes/Digst/Kidney
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Li, Zhongdao; Pearlman, Alexander H; Hsieh, Peggy (2016) DNA mismatch repair and the DNA damage response. DNA Repair (Amst) 38:94-101
Hsieh, Peggy; Pearlman, Alexander H (2015) EGFR inhibits DNA mismatch repair. Proc Natl Acad Sci U S A 112:5556-7
Hsieh, Peggy (2012) DNA mismatch repair: Dr. Jekyll and Mr. Hyde? Mol Cell 47:665-6