Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

When cells experience damage to their DNA they can either repair or bypass it to complete copying of their genetic material. To prevent delaying division, cells often choose to bypass DNA damage and return to repair it later. Cancer cells lacking certain DNA repair pathways or treated with chemotherapeutics co-opt these bypass mechanisms to allow tumors to continue growing and dividing. To re-sensitize these cancer cells to chemotherapy, researchers have developed inhibitors targeting proteins responsible for DNA lesion bypass, known as TransLesion Synthesis (TLS) polymerases. However, we don't understand the precise deficiencies in DNA repair or types of DNA damage that would benefit the most from being treated with TLS inhibitors. To address this, my project will systematically test DNA repair deficient cells in the presence or absence of chemotherapy to determine the genetic characteristics of cancer cells in which inhibiting TLS polymerases would be most effective. Ultimately, this work will inform precision medicine efforts aiming to treat tumors lacking DNA repair activities or experiencing treatment resistance.