Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining.

ABSTRACT: SUMOylation is critical for numerous cellular signalling pathways, including the maintenance of genome integrity via the repair of DNA double-strand breaks (DSBs). If misrepaired, DSBs can lead to cancer, neurodegeneration, immunodeficiency and premature ageing. Using systematic human proteome microarray screening combined with widely applicable carbene footprinting, genetic code expansion and high-resolution structural profiling, we define two non-conventional and topology-selective SUMO2-binding regions on XRCC4, a DNA repair protein important for DSB repair by non-homologous end-joining (NHEJ). Mechanistically, the interaction of SUMO2 and XRCC4 is incompatible with XRCC4 binding to three other proteins important for NHEJ-mediated DSB repair. These findings are consistent with SUMO2 for

SUBMITTER: Cabello-Lobato MJ 

PROVIDER: S-EPMC9071424 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature