ADP-ribosylation in DNA damage response and ageing

Owing to its chemical instability, studying ADPr at the molecular level is very challenging. We have developed an advanced mass spectrometric and computational approach for truly unbiased identification of ADPr sites. This has allowed us to uncover a long and systematically overlooked form of ADPr, called o-glycosidic ADPr, on serine residues (Leidecker et al. Nature Chemical Biology 2016). More, recently we have shown that this novel protein modification is a widespread signal, targeting hundreds of proteins in DNA repair (Bonfiglio et al. Molecular Cell 2017). In addition, we have described the biochemical basis of o-glycosidic ADPr by identifying its “writers” (Bonfiglio et al. Molecular Cell 2017) and its “eraser” (Fontana et al. eLife 2017).

By building upon these seminal discoveries and combining our advanced proteomic methodology with biochemical and cellular approaches, we aim to understand at the molecular level how ADPr regulates DNA repair and the process of ageing.