Mhairi McBride

• BSc (Hons) Biochemistry
• Determination of TIAR foci as an indicator of replication stress for potential ATR inhibitor-induced cytotoxicity in cancer therapy

Cancer cells experience replication stress when their DNA damage response experiences defects. Replication stress is events that take place usually during DNA replication that prevent normal function and stability. To prevent the cells from continuing to divide when the DNA is damaged, (as this could lead to mutations and/or apoptosis (programmed cell death)) a pathway of enzymes, the ATR-CHK1-WEE1 pathway is activated to halt the cell cycle (creation of new cells) before mitosis (cell division/separation) occurs for DNA repair to take place. Therefore, by inhibiting this pathway, the cycle isn’t halted, the DNA isn’t repaired, and apoptosis will occur after division.

This pathway inhibition can be exploited for cancer therapy which is potentially a much safer method as only the cancer cells (those experiencing replication stress) will be targeted so a marker is needed to distinguish these cells from normal cells which is what we are focusing on finding

Funding source: Newcastle University

Project supervisor: Professor Nicola Curtin