Next generation technologies for systematic analysis of DNA structure and repair

The roles of genes, the regulation of their expression, and the interaction of these factors are fundamental components of cellular function. Genomic technologies now allow us to directly assay gene functions and gene expression regulation in an unbiased manner and on a global scale. We have utilized the yeast deletion collection to perform a global survey of genes involved in the DNA-damage response. Each deletion mutant was screened simultaneously against each of 12 functionally distinct DNA-damaging agents to provide a set of screens that resulted in the identification of both new and previously known gene functions and interactions. Going beyond gene function, it is now widely recognized that gene expression regulation is a major factor in phenotypic variation. As an orthogonal view on the cellular system to fitness profiling, we have used a whole genome tiling array to map global nucleosome occupancy in yeast as a step towards understanding the impact of chromatin structure on gene expression regulation on a genome-wide level.