A DNA Integrity Network in the Yeast Saccharomyces cerevisiae

(Cell 124, 1069–1081; March 10, 2006) This paper employed a high-throughput microarray-based screening process (diploid synthetic lethal analysis by microarray [dSLAM]) as an approach for identifying functional modules involved in DNA metabolism. The main conclusions of the paper pertain to the DNA integrity network identified, and these were based on follow-up validation of synthetic lethal or fitness interactions between individually tested pairs of mutations, many of which have subsequently been reproduced by others. It has come to our attention that the Experimental Procedures section did not include sufficient information regarding how mutant pairs were selected for individual follow-up validation. Mutants with 635 nm/532 nm ratios ≥ 2.0 with either uptags or downtags, as well as those with ratios ≥ 1.5 with both tags, were selected. Mutants with only one tag ratio ≥ 1.5 were also selected for genes involved in DNA metabolism or functionally related to the query. In addition, a subset of the interactions validated was not chosen for such validation, based solely on the primary microarray data. Though our original Table S1 provided an indication of this fact, we realize that the statement therein was incomplete. A re-analysis of the original data reveals that the total percentage of interacting pairs selected for validation, based strictly on primary dSLAM data, was ∼75% of the total reported. The rationale for individually testing the remaining validated interaction reported in the paper is as follows: An additional 11% were derived from analysis of dSLAM data of two query mutations known to be related due to either phenotypic similarity or similar patterns of interactors as revealed by dSLAM. Another 11% were detected based on a phenotypic miniarray test (similar to an eMAP) done on a set of genes that were indicated by the dSLAM data and other screens to be part of the larger DNA damage network. About 3% were tested based on other prior knowledge. We regret the omission and note that the subset of interactions whose identification was not based directly on the dSLAM screen cannot be used to support the efficacy of the dSLAM method itself. A revised Table S1 and a supporting data file have been prepared to indicate in which cases information beyond the original dSLAM data was used to select candidates for individual validation. Download .xlsx (.33 MB) Help with xlsx files Table S1. Individually Confirmed Synthetic Lethality or Fitness Defect Interactions, Related to Experimental Procedures Download .xlsx (.04 MB) Help with xlsx files Data S1. Supporting Data for Table S1 A DNA Integrity Network in the Yeast Saccharomyces cerevisiaePan et al.CellMarch 10, 2006In BriefA network governing DNA integrity was identified in yeast by a global genetic analysis of synthetic fitness or lethality defect (SFL) interactions. Within this network, 16 functional modules or minipathways were defined based on patterns of global SFL interactions. Modules or genes involved in DNA replication, DNA-replication checkpoint (DRC) signaling, and oxidative stress response were identified as the major guardians against lethal spontaneous DNA damage, efficient repair of which requires the functions of the DNA-damage checkpoint signaling and multiple DNA-repair pathways. Full-Text PDF Open Archive