Mammalian cells are continually exposed to environmental and endogenous DNA damage that threatens their genomic integrity. Efficient repair of DNA damage is essential for the maintenance of genome stability and preventing diseases associated with compromised genomic integrity, such as cancer and neurodegenerative disease.

Damaged DNA is repaired through a series of coordinated and complex steps involving DNA damage recognition, cell cycle arrest and signaling-induced activation of DNA repair machinery – processes collectively referred to as the DNA damage response (DDR). In the last few years, several chromatin-based events have been shown to be critical mediators of an effective DDR. Whilst it is becoming clear that the chromatin environment is important for the accurate and efficient repair of DNA damage, the key mediators of these events remain poorly defined. The Clarke Lab aims to identify novel chromatin factors involved in DNA damage repair and determine the mechanisms by which these factors maintain genome integrity.

Our research has the potential to identify important mechanistic drivers of a range of human diseases, including cancer, premature aging, and human developmental syndromes. Ultimately, our goal is to leverage our understanding of DNA repair mechanisms to inform new therapeutic strategies for a range of diseases and conditions underpinned by genome instability.