ADP-ribosylation in DNA repair and ageing

Reversible post-translational modifications (PTMs) of proteins control a myriad of key physiological and pathological processes. ADP-ribosylation (ADPr), a PTM of major interest for the research group of Ivan Matic, has attracted much attention due to its biomedical importance in DNA damage response, cancer therapy and ageing. PARP-1, a well-known enzyme that catalyzes protein ADPr, plays a critical role in DNA repair by modifying and recruiting essential chromatin factors, including histones and DNA repair proteins.

Owning to its chemical instability, studying ADPr at the molecular level is very challenging. We have developed an advanced mass spectrometric 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).

By building upon these recent discoveries and combining our top-notch 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.

Third-party funding

  • 2014 - 2021 | CECAD Junior group Leader

  • 2016 - 2018 | Marie Curie Individual Fellowship (to Juan Jose Bonfiglio)
    Decoding the DNA damage signalling in C. elegans by proteomic analyses of ADP-ribosylation

  • 2014 - 2018 | DFG, CECAD grant