Fig. 5: Roles of the “Other” subfamily in DDR and repair.

A AREL1 promotes the ubiquitination and subsequent proteasomal degradation of pro-apoptotic factors, including IAP, SMAC, HtrA2, and ARTS. B HUWE1 targets and destabilizes key oncoproteins such as Dishevelled and C-Myc. It concurrently confers apoptotic sensitivity through its ubiquitin ligase activity on Mcl-1, HDAC2, and Cdc6. Its role in DNA integrity maintenance is highlighted by its interaction with H2AX and BRCA1 in HR repair, and its regulatory effect on NEIL1 in BER. C G2E3 is necessary for an efficient DDR signaling and regulation of mitosis. D TRIP12 significantly influences SSBs repair by modulating the stability or activity of PARP1, while its regulatory impact on ARF underscores its contribution to appropriate cell cycle transitions. Acting on RNF168, TRIP12 also regulates the recruitment of DSBs repair factors. E Additionally, to TRIP12, UBR5 regulates RNF168. UBR5 is involved in DDR, facilitating DNA repair upon replication stress or oxidative stress. It interacts with ATMIN and influences 53BP1 localization for initiating NHEJ. Finally, UBR5 regulates the oxidative stress response through its effect on TXNIP. Arrows indicate activation or promotion of the pathway, while blunt lines denote inhibition.