Polynuclear Ruthenium Organometallic Complexes Induce DNA Damage in Cells Repaired by the Nucleotide Excision Repair Pathways Olivia Fast Faculty mentor: Steven Shell University of Virginia’s College at Wise
Ruthenium organometallic compounds represent an attractive avenue in developing alternatives to platinum-based chemotherapeutic agents. While evidence has been presented indicating ruthenium-based compounds interact with isolated DNA in vitro, it is unclear what effect these compounds exert in cells. Moreover, the antibiotic efficacy of ruthenium organometallic compounds remains uncertain. In this study we report that exposure to polynuclear ruthenium organometallic compounds induces recruitment of damaged DNA sensing protein Xeroderma pigmentosum Group C (XPC) into chromatin-immobilized foci. Additionally, we observed one of the tested polynuclear ruthenium organometallic complexes displayed increased cytotoxicity against human cells deficient in nucleotide excision repair (NER). Taken together, these results suggest that polynuclear ruthenium organometallic compounds induce DNA damage in cells, and that cellular resistance to these compounds may be influenced by the NER DNA repair phenotype of the cells. Olivia Fast is a third year biochemistry major from Pound, Virginia. She plans to attend dental school after graduation.
