Genome Integrity

Professor Jiri Bartek

Cells employ an extensive network of DNA damage response (DDR) processes to protect genome integrity and promote survival after exposure to genotoxic stresses. Distinct DNA repair pathways respond to different types of damage, while cell cycle checkpoints provide the time that is needed to repair DNA lesions (Jackson and Bartek, 2009).

Cancer is one of the many diseases that is caused by malfunctions of the DDR. Therefore, the combined DNA repair pathways and cell cycle checkpoints act as a highly interlinked anti-cancer barrier, which can be compromised by functional loss of individual DDR factors due to mutations.

Because many cancer treatments are based on DNA damaging agents to kill cancer cells, it is of high importance to understand which DDR pathways are disrupted to what extent in individual patients in order to provide the right dose and drug. Additionally, in some cases misregulation of a single gene can determine survival or death in response to genotoxic treatment (Fagerholm et al., 2008).

Similarly, mutation of individual DDR members, which guard the entry into the cell cycle, can strongly affect the cellular differentiation status, as the ablation or sustained deactivation of cell cycle repressors contributes to the cancer cells’ intrinsic tendency to dedifferentiate (Strauss et al., 2012).