Determining the roles of the Artemis nuclease in genome stability at the replication fork

Damage to DNA occurs constantly within our cells. If this damage is not repaired, it can lead to mutations in our genome when cells divide, which can cause cancer. So, to protect the integrity of our DNA, cells have evolved a variety of mechanisms to fix these lesions.

One protein that plays a key role in these processes is Artemis, which acts in the repair of several different forms of damage by incising sections of damaged DNA. I will study this protein using a range of biochemical, genetic and cell biology techniques.

These will characterise the reactions that Artemis catalyses at sites of DNA damage, whether it requires interacting partners or modifications to do so and will enhance our understanding of the functions of each of its domains. I will also be collaborating with chemists to develop inhibitors against Artemis.

By better understanding the mechanisms that protect our DNA at the molecular level, we can improve cancer treatments.

Chemotherapeutic drugs often kill tumour cells by damaging their DNA and cancers can evolve resistance to these treatments by increasing their capacity for repair.

Inhibitors targeting Artemis could therefore be used to help overcome resistance to chemotherapeutic drugs and radiotherapy.