Figure 1.

Ubiquitination regulates DSB repair pathway. (A) DSBs can be repaired by NHEJ and HR. Both pathways initiate with recruitment of MRN complex and E3 ubiquitin ligases RNF8 and RNF168. DNA repair pathway choice is determined by recruitment of 53BP1 or BRCA1 in H2A. 53BP1 leads NHEJ in G1 phase, whereas BRCA1 leads HR in S/G2 phase. (B) In NHEJ, Ku recruits DNA-PKcs. 53BP1 that phosphorylated by ATM binds with PTIP and RIF1. 53BP1 and PTIP recruit Artemis, which trims the DNA ends. Additional NHEJ factors assemble and ligate DNA breaks. During NHEJ, HR is suppressed through ubiquitin-mediated degradation of CtIP by APC/C^Cdh1 and inhibition of BRCA1 by 53BP1-RIF1 and CRL3^KEAP1. (C) In HR, RNF138 ubiquitinates Ku for degradation. BRCA1, MRN, and CtIP form a complex, and ubiquitinated CtIP takes part in end resection. Then, ssDNA tail is bound by RPA. When PALB2 is deubiquitinated by USP11, BRCA1-PALB2-BRCA2 complex mediate replacement of RPA into RAD51. RAD51-coated filaments invade the homologous strand. Finally, DNA synthesis is completed with ubiquitin-mediated degradation of RAD51 by RFWD3. During HR, NHEJ is suppressed through inhibition of 53BP1 by BRCA1.