A lot of cellular protein activities are quickly regulated by reversible post-translational modifications. We are, in particular, interested in the regulatory role of poly-ADP-ribosylation (PARylation), a NAD-dependent modification carried out by poly-ADP-ribose polymerases (PARPs). PARP1 – the founding member of the PARP family – is rapidly recruited to sites of DNA damage and locally produces poly-ADP-ribose polymer, most of which is attached to PARP1 itself. A number of proteins are targets of PARylation, among them histones and other chromatin components. PARylation regulates a wide array of cellular functions from DNA repair, chromatin structure to gene-expression.
We use a combination of live-cell imaging, high-content screening and enzymatic assays to identify novel regulators of chromatin and the way signaling networks modulate them during the DNA damage response and develop a mechanistic description of these regulatory networks.