Evaluation of: Lee W, St Onge RP, Proctor M et al.: Genome-wide requirements for resistance to functionally distinct DNA-damaging agents. PLoS Genet. 1(2), e24 (2005). Despite intense study, the mechanistic and therapeutic differences in cellular responses to DNA-damaging agents are not fully understood. In order to expand knowledge of DNA damage, the authors of this study assayed the effects of 12 anticancer agents on the complete pool of approximately 4700 homozygous deletion strains of Saccharomyces cerevisiae. The screens identified genes in well-characterized DNA, in addition to genes whose role in DNA-damage-response pathways had not previously been established.