Web supplement to
"Genome-wide requirements for resistance to functionally distinct DNA damaging agents"

William Lee*, Robert P. St.Onge*, Michael Proctor, Pat Flaherty, Adam P. Arkin, Ronald W. Davis, Corey Nislow, and Guri Giaever.

DNA Damage Response


This study focused on the effects of covalent DNA binding compounds on the growth and viability of mutant yeast strains. This website provides access to the raw and analyzed data generated in this study, as well as additional useful supplementary information. Data can be accessed in 3 ways:

  1. Fitness Defect scores for each deletion strain in each of the 36 array experiments performed for this study. This can be downloaded as one composite file or searched on an individual ORF/gene basis.
  2. Growth curve data for a subset of deletion strains grown in 96-well plates in the presence of DMSO and mechlorethamine.
  3. Raw intensity values for individual features on each of the arrays.

Cover art designed by Trine Giaever


The mechanistic and therapeutic differences in the cellular response to DNA damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we examined the effects of 12 DNA damaging agents on the complete pool of ~4700 nonessential, barcoded homozygous diploid deletion strains of Saccharomyces cerevisiae. In our protocol, a pool of barcoded homozygous deletion strains is grown competitively in the presence of compound. Individual strain abundance is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. Extrapolation of the resulting signal intensities allows determination of the relative sensitivity of each strain in the pool. These screens identified genes involved in well characterized DNA damage response pathways including nucleotide excision repair, homologous recombination repair, and cell cycle checkpoint control. We also uncovered genes whose role in the DNA damage response was not previously established. Each compound produced a unique genome-wide profile, both with respect to the magnitude of strain sensitivity and to the temporal response of different deletion strains to different treatment. Analysis of these data allowed us to determine the relative importance of DNA repair modules for resistance to each of the 12 profiled compounds. Comparing and clustering the data for 12 distinct compounds uncovered both known and potentially novel functional interactions that comprise the DNA damage response.

Inquiries can be addressed to ggiaever@stanford.edu.