DNA can be damaged by various sources including UV light, chemicals and radiation, as well as from errors resulting from the molecular mechanisms inside our cells. If this DNA damage goes unrepaired then mutations can arise which can lead to cancer. Our cells have mechanisms to detect DNA damage and repair it in a process known as the DNA damage response. Understanding how this mechanism works is crucially important in understanding how cancer develops and progresses.
In addition, many cancer treatments are DNA damaging agents that act to kill rapidly dividing cells so understanding these pathways can help us to develop cancer therapies and also understand the impact of existing therapies on both cancer cells and normal cells.
DNA in our chromosomes is packed via histone proteins into a complex known as chromatin. One such histone protein, which plays an important role in the DNA damage response, is H2AX. This protein plays a role in the recruitment and retention of repair factors at DSBs sites.
Correlation between H2AX status and the effectiveness of the DNA damage response is of particular interest in cancer cells since further DNA damage can lead to metastasis and tumour progression.
Research in my lab is investigating the status of H2AX copy number, gene expression and protein abundance in cell lines derived from cancer patients and also in clinical biobank samples.
DNA double stand breaks are one of the most problematic types of DNA damage and in my lab we are interested to understand the dynamic nature of chromatin during the process of DNA damage recognition and repair. Since these cellular process happen very rapidly (in the range of <10 seconds to 10 minutes) we are developing tools to study the DNA damage response in real time using live cell imaging (Fig. 1).