A common strategy organisms have for controlling biological processes in a cell is to decorate important proteins with a chemical tag, such as a phosphate, methyl, or acetyl group. One of the most complex and fragile of these so-called posttranslational modifications is known as adenosine diphosphate ribosylation, or ADPr. This modification is used by many pathogens, including the causative agent of cholera, which uses ADPr to orchestrate lysis of intestinal cells. In mammals, the tag is involved in DNA repair, and malfunctions in ADPr decoration can lead to cancer. Despite ADPr’s importance, researchers know little about its precise molecular mechanisms or the specific amino acids ADPr decorates. To remedy this situation, a team led by Ivan Matic of the Max Planck Institute for Biology of Ageing has developed a mass spectrometry technique to identify and quantify ADPr in cells (Nat. Chem. Biol. 2016, DOI: 10.1038/nchembio.2180). The method reveals that histone proteins are tagged with ADPr on serine residues in response to DNA damage. “This work provides both a new direction of inquiry into the role of ADPr in cellular function and a new tool with which to explore it,” the researchers note.