Structural mechanism of multi-faceted roles of DNA helicases in cellular DNA repair, replication, and transcription.

DNA helicases play essential roles in cellular DNA repair, replication, and transcription to maintain genome stability.

This PhD project focuses on understanding how certain DNA helicases and their related complexes assemble at the sites of DNA damage to resolve the tangled DNA local structures (e.g.

G-quadruplex DNA and DNA-protein crosslinks) when these structures block the progression of replication or transcription.

To achieve this goal, we combine cutting-edge techniques such as cryo-EM, structural mass spectrometry and single-molecule studies to visualize their structures and characterize their time-resolved functions. This study will expand our fundamental understanding of DNA damage response at a molecular level in healthy cells.

However, the long-term applications of this knowledge will be to understand how these decisions go wrong in cancer cells. Ultimately, we want to exploit these differences to develop drugs that can kill cancer cells specifically.