collected picture

Research Focuses:

* Structural characterization of macromolecules for understanding their functions by X-ray crystallography.
* Drug development based on structural studies of substrate-target complexes.

Current Projects:

Structural study on key proteins in translesion DNA synthesis Translesion DNA replication or translesion synthesis (TLS), the extension of primers across damaged DNA templates, is a fundamental process used by a cell to survive DNA damage. High-fidelity replicative polymerases are unable to bypass damaged DNA and are therefore stopped by lesions. To avoid deleterious consequences of replication fork collapse, cells employ specialized DNA polymerases to continue replicating through the damaged DNA. Most of the so-called translesion polymerases belong to the recently identified Y-family of DNA polymerases. These unique DNA polymerases are characterized by their ability to bypass lesions and by their low fidelity in DNA replication. Thus, TLS is also a major source of point mutations that is associated with the onset of human diseases, such as cancer. Current research focuses in the lab are:
         • Determination of X-ray structures of a series of complexes of Y-polymerase Dpo4 and DNA fragments containing lesions and mismatches to decipher the specificity of the Y-polymerase.
         • Structural study of specific interactions between translesion Y-polymerase Dpo4 and its co-factor PNCA to explore the mechanism of DNA polymerase recruitment on the replication fork.
         • Structural study of Dpo4 in complex with DNA adducts that are associated with cancer and anti-cancer drug resistance.


Research Funded by:

  Canadian Institutes of Health Research   National Cancer Institute of Canada     Terry Fox Foundation   Canadian Foundation of Innovation   Ontario Innovation Trust     Ontario Early Research Award       Cancer Research Society  
Ling Lab Department of Biochemistry University of Western Ontario