UV-B radiation in sunlight has diverse effects on humans, animals, plants, and microorganisms. UV-B can cause damage to molecules and cells, and consequently organisms need to protect against and repair UV damage to survive in sunlight. In plants, low nondamaging levels of UV-B stimulate transcription of genes involved in UV-protective responses. However, remarkably little is known about the underlying mechanisms of UV-B perception and signal transduction. Here we report that Arabidopsis UV RESISTANCE LOCUS 8 (UVR8) is a UV-B-specific signaling component that orchestrates expression of a range of genes with vital UV-protective functions. Moreover, we show that UVR8 regulates expression of the transcription factor HY5 specifically when the plant is exposed to UV-B. We demonstrate that HY5 is a key effector of the UVR8 pathway, and that it is required for survival under UV-B radiation. UVR8 has sequence similarity to the eukaryotic guanine nucleotide exchange factor RCC1, but we found that it has little exchange activity. However, UVR8, like RCC1, is located principally in the nucleus and associates with chromatin via histones. Chromatin immunoprecipitation showed that UVR8 associates with chromatin in the HY5 promoter region, providing a mechanistic basis for its involvement in regulating transcription. We conclude that UVR8 defines a UV-B-specific signaling pathway in plants that orchestrates the protective gene expression responses to UV-B required for plant survival in sunlight.photomorphogenesis ͉ ultraviolet-B radiation ͉ UV RESISTANCE LOCUS 8 U V-B radiation (280-320 nm) is an integral component of sunlight. UV-B can cause damage to macromolecules, including DNA, and generate reactive oxygen species. Because UV-B affects the growth, development, reproduction, and survival of many organisms, there is concern that any further increases in ambient levels of UV-B, resulting from stratospheric ozone depletion may have a significant impact on natural and agricultural ecosystems (1-4). Hence, it is important to understand how plants and other organisms protect themselves against the potentially damaging effects of UV-B.Exposure to UV-B is obligatory for higher plants because of the need to maximize light capture for photosynthesis. The effects of UV-B on diverse species of plants have been reported in the literature, and it is evident that different responses are observed at different UV-B fluence rates (5, 6). Exposure to high amounts of UV-B causes tissue necrosis and induces the expression of stressassociated genes in part through activation of pathogen-defense and wound-signaling pathways (5-7). At ambient UV-B levels, crosstalk between wound and UV-B signaling pathways modifies plantinsect interactions (8). Importantly, exposure to low nondamaging levels of UV-B has numerous regulatory effects on plant morphology, development, physiology, and biochemical composition (1,5,6,9). Low fluence rates of UV-B promote the expression of a range of genes involved in UV-B protection (5, 6, 10, 11). These include genes c...