2025/12/01 by Jai S. Bhachoo, Alexander J. Garvin · 1 voice
Biochemistry, Genetics and Molecular Biology · #Cell death mechanisms and regulation #DNA Repair Mechanisms #Ubiquitin and proteasome pathways
paper · pdf · doi:10.1042/ebc20253043
openalex publication_date 2025/12/01 · openalex created_date 2025/12/12 · openalex updated_date 2026/07/02
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.