KNAW Heineken Lecture

Steve Jackson @Leiden: Cellular responses to DNA damage: mechanistic insights and applications in cancer therapy

26 September 2016 from 16:00 to 17:00 hrs
Leids Universitair Medisch Centrum, Lecture Hall 1, Gebouw 1, Albinusdreef 2, Leiden
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Lecture by Steve Jackson, laureate of the Dr A.H. Heineken Prize for Medicine 2016

Abstract of the lecture

At rest, each human cell sustains tens of thousands of DNA lesions per day. Furthermore, additional DNA damage can be induced by a range of environmental agents, including man-made chemicals and ionizing radiation. To combat such threats to genome stability, our cells have evolved elaborate ways to detect, signal the presence of and repair DNA damage. The importance of these processes is highlighted by inherited or acquired defects in them causing various human pathologies, such as immune-deficiencies, neurodegenerative diseases, premature ageing and cancer. Moreover, our increasing knowledge of cellular DNA-damage responses is providing opportunities for developing novel classes of drugs to treat cancer and other age-related diseases.

Much of the work in my laboratory aims to decipher the mechanisms by which cells respond to and repair the most toxic of all DNA lesions: DNA double-strand breaks (DSBs). Most of our work in this area addresses the functions of proteins that mediate such mechanisms, and the generation and molecular functions of post-translational modifications (PTMs) on DSB-responsive proteins.

In this talk, I will highlight some of our work showing how various PTMs control important transitions in DDR-protein-complex assembly and disassembly, and how such events promote genome stability. I will also describe how our past and present work is providing opportunities for developing novel anti-cancer agents as well as explaining how cancer cells can evolve resistance to certain therapeutic agents. Finally, I will explain how such work is also providing paradigms for better understanding various other human diseases as well as identifying potential new therapeutic strategies for such diseases.