DNA becomes damaged upon exposure of cells to high-energy radiation and mutagenic chemicals prevalent in our environment. These agents, along with replicative stress, endogenous oxygen radicals, and reactive aldehydes, pose a constant threat to maintaining a stable genome. Of the myriad DNA lesions, the DNA double-strand break (DSB) is among the most harmful because of its potential to cause deletions and other gross chromosome rearrangements. Accordingly, failure to properly resolve DSBs can lead to cellular transformation, cancer, and other pathologies, such as intellectual impairment and neurological disorders. Dysregulation of DSB repair pathways is a significant cause of innate and acquired resistance to cancer therapy.
The elucidation of DSB repair mechanisms will significantly impact health sciences. It will also provide insights to guide protection against DNA damage, explain drug resistance in cancer therapy, and identify new targets for developing novel therapeutics tailored to the DSB repair status in cancer patients.
Our laboratory investigates the mechanistic underpinnings of DSB repair mechanisms, particularly in the homology-directed DNA repair (HDR) pathway, which plays a critical role in the error-free elimination of DSBs and replication fork repair (Figure below). Our research harnesses various biochemical, biophysical, and cell biological analytical tools to interrogate HDR factors at the molecular and cellular level, and to draw a comprehensive picture of the HDR machinery.
Learn more about Dr. Sung’s research.