Abstract

Inherited or acquired defects in detecting, signalling or repairing DNA damage are associated with various human pathologies, including immunodeficiencies, neurodegenerative diseases and cancer(1). Work in my laboratory aims to decipher the mechanisms by which cells detect DNA damage, signal its presence and mediate its repair(2). Much of our work focuses on DNA double-strand breaks (DSBs) that are generated by ionizing radiation and radiomimetic chemicals, and which also arise when the DNA replication apparatus encounters various forms of DNA damage. In this talk, I will summarize how our recent work has helped to establish how protein complexes assemble and disassemble on chromatin at sites of DNA damage and how these complexes promote DNA repair and DNA -damage signalling. I will also explain how our increasing knowledge of cellular DNA -damage responses is providing exciting opportunities for developing novel treatments for cancer(3). Finally, I will describe how the Cambridge-based company MISSION Therapeutics (http://www.missiontherapeutics.com/) plans to exploit these opportunities to produce new, more effective anti-cancer medicines.

References 1. Jackson, S.P. and Bartek, J. (2009). The DNA -damage response in human biology and disease. Nature 461, 1071-1078. 2. Polo SE and Jackson SP. (2011). Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev. 25, 409-433. 3. Jackson, SP. (2009). The DNA -damage response: new molecular insights and new approaches to cancer therapy. Biochem. Soc. Trans. 37, 383-394