Dr. Mark Muller


A large number of anti-cancer chemotherapeutics target DNA topoisomerases. Etoposide is a specific topoisomerase II poison that causes reversible double strand DNA breaks. This project analyses the repair of DNA damage induced by etoposide, a common anti-cancer chemotherapeutic. Through the comparison of two known DNA repair pathways, anti-cancer chemotherapy may become more cytotoxic. Double strand DNA break repair is mediated by either non-homologous end joining (NHEJ) or homologous recombination (HR). NHEJ repairs through direct ligation of a double stranded break, whereas HR utilizes a homologous template to recover the wild type sequence. Reporter cassettes involving the expression of green fluorescent protein were used to distinguish between these repair mechanisms. Titrations with etoposide show that a logarithmic increase in drug concentration yields a corresponding increase in repair through HR. This result demonstrates that topoisomerase II mediated damage is efficiently repaired by the process of HR. Additional experiments with another reporter cassette indicated that repair of topoisomerase II mediated DNA damage occurs more efficiently through the HR pathway than the NHEJ pathway. Collectively, the data suggest that tumor cells proficient in HR repair may effectively elude treatment by topoisomerase II targeting drugs.

About the Author

Eric Goldstein attended the University of South Florida from 2007 to 2008, where he worked in an organic chemistry lab, before transferring to the University of Central Florida in 2008. At UCF, Eric worked as an undergraduate researcher in Dr. Mark Muller's laboratory and presented at the Showcase of Undergraduate Research Excellence in 2011, for which he received an Honorable Mention. Eric will graduate from the Wayne State University School of Medicine in 2015.



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