DNA double strand break repair: a model of specificity and complexity in SUMO signalling

Among the ubiquitin-like superfamily, small ubiquitin-like modifiers (SUMOs) are the most well-understood. However, in comparison with the prototypical small modifier ubiquitin, our understanding of the SUMO system lags. SUMOylation is often characterised as ‘simple’ in comparison with ubiquitination, with fewer SUMO-specific writers, readers and erasers compared with the ubiquitin machinery. A key divergence between ubiquitin and SUMO is that the SUMOylation system utilises a group of related SUMOs (SUMO1– 5), each possessing distinct functions. SUMO paralogs share conjugation, recognition and deconjugation machinery, yet signalling can employ each to perform specific cellular functions. This illustrates a complex layer of molecular discrimination that is far from simple. The repair of DNA double-stranded breaks (DSBs) – highly toxic DNA lesions generated from both endogenous and external sources – serves as a fascinating exemplar of specificity in SUMO signalling. This review focuses on how signalling specificity is achieved during SUMO-DSB repair. Examples of how different branches of SUMO signalling can direct discrete DSB-repair outcomes through modulation of key repair factors, including the RAP80-BRCA1-A complex, RNF168 and CtIP, are described in further detail.