Project Summary This F31 NRSA application focuses on characterizing the mechanisms of a novel oncogene. I am requesting support for developing a project which I have previously initiated. This proposal addresses a fundamental gap in knowledge and could vitally affect cancer therapeutics and cancer patients. Moreover, this application would greatly impact my graduate school training, as well as my long-term goal of becoming an independent academic research scientist. This proposal would allow me to acquire a complex mix of skills, some of which I have already developed during my time here at Penn State Hershey, and some that are new but highly attainable due to the support and resources available to me at Penn State Hershey. In this proposal, I focus on determining the mechanisms of DNA replication stress resistance and cellular transformation observed in cells upon PARP10 overexpression. My recent publication in Nucleic Acids Research lays out a great foundation for the role of PARP10 in cancer. Here, I hope to expand this research to obtain a mechanistic view of this process, to reduce this gap of knowledge and gain information relevant for this novel oncogene. Due to its abundance in patient tumors, PARP10 could be a novel therapeutic target. To investigate the roles of PARP10 further, I will explore 2 aims: 1) Investigation of PARP10 components and their role in replication stress resistance, and 2) investigation of PARP10 components and their role in cellular transformation. Achieving these aims will expand my knowledge and independent thinking as a young scientist. Not only will this work advance my personal goals, but it will also significantly impact the field by providing relevant information about this potential therapeutic target.