InterPro domain: IPR027786

Proteins in the NSE4/EID (Non-structural maintenance of chromosomes element 4/EP300-interacting inhibitor of differentiation 3) family are components of the Smc5/6 complex that is involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination and mediates sumoylation of shelterin complex (telosome) components [ 1 , 2 , 3 ]. In human, it acts as a repressor of nuclear receptor-dependent transcription possibly by interfering with CREBBP-dependent coactivation. It may function as a coinhibitor of other CREBBP/EP300-dependent transcription factors [ 4 ].

Interestingly, there is a single NSE4 gene in most eukaryotes up to non-placental mammals while there are several NSE4/EID copies in placental mammals [ 4 ]. In humans, there are two NSE4 proteins, NSE4a and NSE4b/EID3. They contain both N and C-terminal kleisin domains. Their N-terminal domain binds to SMC6 neck and bridges it to the SMC5 head [ 5 ] and to the Nse3 (another SMC5-6 complex subunit) pocket [ 6 ], which seems to increased the stability of the ATP-free SMC5/6 complex.

1. EID3 is a novel EID family member and an inhibitor of CBP-dependent co-activation. Nucleic Acids Res. 33, 3561-9
2. Qri2/Nse4, a component of the essential Smc5/6 DNA repair complex. Mol. Microbiol. 55, 1735-50
3. The Smc5/6 complex is required for dissolution of DNA-mediated sister chromatid linkages. Nucleic Acids Res. 38, 6502-12
4. Analysis of the Nse3/MAGE-binding domain of the Nse4/EID family proteins. PLoS ONE 7, e35813
5. A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6. Sci Rep 10, 9694
6. Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families. PLoS ONE 6, e17270