No abstract

Highlights d The E3 ubiquitin ligase RNF168 supports BRCA1independent homologous recombination d RNF168 acts redundantly with BRCA1 to load PALB2 onto damaged DNA d Targeting RNF168 could induce synthetic lethality in BRCA1deficient cancers d The function of BRCA1 in replication fork protection is separable from its HR role

Highlights d 53BP1 S25A point mutation rescues lethality of BRCA1 D11 mice without restoring HR d 53BP1 S25A mutation uncouples 53BP1 end-blocking activities pre-and post-resection d RIF1/shieldin blocks BRCA1-independent loading of RAD51 onto single-strand DNA d Shieldin and PTIP associate with 53BP1 to regulate distinct end-resection pathways