Opposing roles of RNF8/RNF168 and deubiquitinating enzymes in ubiquitination-dependent DNA double-strand break response signaling and DNA-repair pathway choice

The e3 ubiquitin ligases ring finger protein (rnf) 8 and rnf168 transduce the dna double-strand break (dsb) response (ddr) signal by ubiquitinating dsb sites. the depletion of rnf8 or rnf168 suppresses the accumulation of dna-repair regulating factors such as 53bp1 and rap80 at dsb sites,suggesting roles for rnf8- and rnf168-mediated ubiquitination in dsb repair. this mini-review provides a brief overview of the rnf8- and rnf168-dependent ddr-signaling and dna-repair pathways. the choice of dna-repair pathway when rnf8- and rnf168-mediated ubiquitination-dependent ddr signaling is negatively regulated by deubiquitinating enzymes (dubs) is reviewed to clarify how the opposing roles of rnf8/rnf168 and dubs regulate ubiquitination-dependent ddr signaling and the choice of dna-repair pathway. © 2016 the author 2016. published by oxford university press on behalf of the japan radiation research society and japanese society for radiation oncology.