Modeling DNA Adducts as Cancer Diagnostic and Therapeutic Markers: Computational Chemistry Studies of the Structure-Function Relationships of DG-C8-A?C Adducts

Recent nucleic acids research has focused on the formation of genotoxic DNA adducts as covalent modifications of DNA that often result from carcinogen exposure; human-made chemicals can also cause DNA damage through bulky DNA adduct formation. DNA adducts are not only markers of carcinogenic exposure but also alter the regulation of oncogene transcription and standard DNA replication. A potent DNA adduct of A?C, a carcinogenic heterocyclic aromatic amine produced in high quantities in tobacco smoke, has been identified (dG-C8-A?C), but the exact pathways and outcomes of its replication by different DNA translesion polymerases involved in DNA repair remain largely unknown. Accordingly, they will be investigated with standard computational chemistry, namely density-functional theory and molecular dynamics simulations, to shed light on the structure-function of these bulky DNA adducts and their mutational signature associated with several cancers, yielding crucial information to exploit them as diagnostic or therapeutic markers of cancer.

Faculty Supervisor:

Gilles Peslherbe

Student:

Partner:

Henan University of Technology

Discipline:

Physics

Sector:

Education

University:

Concordia University

Program: