Dr Marcin Suskiewicz

From

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

In residence at

Molecular Biophysics Center (CBM) / CNRS - FR

Host scientist

Dr Bertrand Castaing

PROJECT

Ubiquitin’s Secretive Sibling: Sumo E3 Ligases & Sumo-Dependent Complex Formation In Dna Repair And Beyond

Faithful transmission and expression of genetic information requires continuous repair of DNA damage that is achieved through numerous pathways. These repair processes are among the most highly coordinated cellular events, with various factors being recruited and released or switched on and off in the right location and order. Such fine temporal and spatial regulation is best achieved by protein post-translational modifications, which reversibly regulate protein function. In this project, I aim to investigate one post-translational modification that is important for DNA repair and many other cellular processes: protein SUMOylation. This sophisticated process involves chemically "decorating" various protein substrates with copies of a small protein, SUMO, that is attached to side chains of lysine amino-acid residues.

As the current knowledge of SUMOylation comes primarily from cellular studies, the structural-mechanistic detail of many of its aspects is lacking. In particular, we would like to better understand how SUMO modification is achieved (SUMO ligation catalysed by SUMO E2 and E3 enzymes) and what its consequences are (SUMO-dependent formation of protein complexes). To address these topics, we will focus on SUMO-dependent regulation of DNA repair, which will serve as a model system but also a fascinating and highly medically relevant process in its own right. Indeed, many DNA repair pathways are being proposed as promising pharmacologic targets in cancer and neurodegenerative diseases.