ADP-ribosylation is a reversible post-translational modification of proteins, which regulates many cellular processes, including DNA damage repair, DNA replication, transcription, cell division and various stress responses. Even though the critical role of ADP-ribosylation in cellular responses to DNA damage has been recognised for several decades, which residues/sites in proteins are ADP-ribosylated and how this signalling is regulated are not well understood. Recently, the Ahel group has uncovered that a newly identified form of ADP-ribosylation (ADP-ribosylation on serine residues) is the major DNA damage-responsive modification of histones and many other proteins involved in genome stability (Palazzo et al., 2018). The group also elucidated how serine ADP-ribosylation is synthesised (by the PARP/HPF1 complex: Gibbs-Seymour et al., 2016; Bonfiglioet al., 2017) and how it is reversed in cells (by the hydrolase ARH3: Fontana et al., 2017).
“It was a great relief to hear we have been awarded this grant,’ said Ivan Ahel. ‘It’s also really exciting as now we can go deep into understanding how ADP-ribosylation is controlled mechanistically and exploring the physiological pathways it regulates.”
To learn more about research done by the Ivan Ahel’s group, please visit the following websites:
Departmental webpage: https://www.path.ox.ac.uk/content/ivan-ahel
Ivan Ahel’s group website: http://ivanahellab.wixsite.com/ivan-ahel-lab
For more information about Wellcome Senior Research Fellowship, check out this link: https://wellcome.ac.uk/funding/senior-research-fellowships-basic-biomedical-science
Written by Sheng Kai Pong