Associate Professor, Eppley Institute
Tel: 402-559-7018 (Office),
DNA interstrand crosslink repair in mammalian cells
Summary of Research
A defect in DNA repair in humans often results in genomic instability and consequently the development of cancer. We are interested in understanding the molecular mechanism of DNA interstrand crosslink (crosslink) repair in mammalian cells. Crosslinks are generated by the widely used chemotherapeutic agents such as cisplatin and enhanced removal of crosslinks is partly attributed to acquired drug resistance during chemotherapy. Another important aspect of our research is the relation between a defect in crosslink repair and development of cancer. The cell lines derived from the cancer-prone hereditary diseases, Fanconi anemia (FA) and the familial breast cancers who have mutations in BRCA2 gene, are highly sensitive to DNA crosslinking agents and many other mutant cell lines which are highly sensitive to DNA crosslinking agents display severe genomic instability. Thus, a defect in crosslink repair may cause genomic instability, which may result in formation of cancer. Our research will be valuable to understand for both cancer-prone genetic defects and cancer chemotherapy.
Currently, we are defining the roles of (1) DNA repair endonuclease, XPF/ERCC1 complex and (2) double strand break (DSB) repair proteins including Rad51 paralogs and Brca2 in crosslink repair using cell free crosslink repair assay. Our long-term goal is to reconstitute crosslink repair with purified DNA repair factors in vitro.