Stress-Free with Rpd3: a Unique Chromatin Complex Mediates the Response to Oxidative Stress

Abstract

Eukaryotic cells are constantly bombarded with a plethora of extracellular and intracellular stresses that they must quickly respond to in order to survive (1). These stresses can come in the form of changes in temperature, nutrient availability, osmotic changes, and DNA-damaging events (extracellular), as well as ox- idative stress from normal metabolism and replicative/transcrip- tional DNA damage (intracellular). In order to respond to a wide range of stresses, cells must be able to rapidly translate a stress response signal into a specific transcriptional program (2). While there are some common themes that underlie the general “envi- ronmental stress response” (ESR), the transcriptional programs each stressor initiates are unique and tailored to deal with each specific type of stress (3). The exact mechanisms underlying the cellular response to a particular stress are poorly defined and con- tinue to be an exciting area of active research. A question of particular significance is how the cell is able to modulate the chromatin environment surrounding the genes nec- essary to respond to specific stresses encountered by the cell. This is a complex problem, as many genes may need to be quickly, and precisely, up- or downregulated in response to each particular type of stress (3). In order to achieve this level of control, the cell must utilize one or more signaling cascades activated by the stres- sor to alter the chromatin landscape precisely at many genomic loci by recruiting a host of chromatin-modifying enzymes (4). It is likely that the posttranslational modifications (PTMs) created by these enzymes form a chromatin signature, or code, that can help to initiate the ESR through recruitment of chromatin effector pro- teins that dock on these histone PTMs (5–8). In this issue of Mo- lecular and Cellular Biology, using Saccharomyces cerevisiae, Baker and colleagues (9) explore a connection between a complex con- taining the histone deacetylase Rpd3 and the ESR pathway, thereby increasing our understanding of how cell signaling and chromatin come together to regulate the cellular response to stress. As described below, these studies break new ground and give rise to many fascinating new questions that await future dis- coveries.