Protecting DNA from damage is essential for the survival of normal cells under different kinds of stress, including during treatments of patients with anticancer therapeutics. Our recent studies suggest that signals originating in the cell's nucleolus play an important role in reducing the extent of drug-induced cellular DNA damage. Through this research, we hope to learn how targeting the nucleolus can be exploited to modulate cell resistance to chemotherapeutic drugs and thus improve the efficiency of cancer treatments.