The Department of Biomedicine

BBB seminar: Ivan Ahel

ADP-ribosylation signalling in regulation of genome stability

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Ivan Ahel,
Sir William Dunn School of Pathology, University of Oxford, UK

We utilise biochemistry, structural biology, cell biology and animal models to study pathways and protein functions underlying genome stability, and which are regulated by a nucleotide type of protein modification called ADP-ribosylation. The major family of enzymes that synthesizes ADP-ribosylation are poly(ADP-ribose) polymerases (PARPs). PARPs utilise nicotinamide adenine dinucleotide (NAD+) as a substrate and modify specific protein targets to control wide range of processes including DNA damage repair, transcription, cell differentiation, metabolism and immune responses. Mammalian PARPs that regulate DNA damage response are PARP1 and PARP2 and they represent important drug targets in cancer therapy. Here we provide new insights into how PARPs regulate DNA damage response and describe several novel regulators of this signalling pathway. In another study, we describe PARP-like toxin-antitoxin systems in bacteria that target DNA (as opposed to proteins) for reversible ADP-ribosylation.

Chairperson: Mathias Ziegler, Department of Biomedicine