A wide-ranging cellular response to UV damage of DNA.

The kinases ATM and ATR are central to proper function of the DNA damage response. These kinases phosphorylate proteins to coordinate cell cycle progression and DNA damage repair/bypass. We have recently reported a large-scale identification of ATM/ATR substrates phosphorylated in response to UV damage of DNA. Overall 231 sites of phosphorylation were induced by UV damage of DNA or dependent on proper function of ATR. The study expanded the number of phosphorylation sites from protein classes known to be involved in the DNA damage response. Further, many sites were identified from protein types not thought to have a role in damage signaling. This observation suggests that the DNA damage response affects a much wider range of cellular processes than was previously appreciated. This study has also extended the successful use of the PhosphoScan proteomic method from phospho-tyrosine to serine/threonine motifs, providing a general blueprint to use the method to study signaling pathways underlying a wide range of diseases.