SMC5 is a core component of the SMC5-SMC6 complex [, ], a complex involved in repair of DNA double-strand breaks by homologous recombination [, ]. In humans, the SMC5-SMC6 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 in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs) []. SMC5 is required for sister chromatid cohesion during prometaphase and mitotic progression; the function seems to be independent of SMC6 [].
Nse4 is the kleisin component of the Smc5/6 DNA repair complex. It bridges the heads of Smc5 and Smc6 []. This entry represents the highly conserved C-terminal domain which interacts with the head domain of Smc5 [].
The structural maintenance of chromosomes (SMC) proteins are large (approximately 110 to 170kDa), and each is arranged into five recognizable domains. Amino-acid sequence homology of SMC proteins between species is largely confined to the amino- and carboxy-terminal globular domains. The amino-terminal domain contains a 'WalkerA' nucleotide-binding domain (GxxGxGKS/T), which by mutational studies has been shown to be essential in several proteins. The carboxy-terminal domain contains a sequence (the DA-box) that resembles a 'Walker B' motif, and a motif with homology to the signature sequence of the ATP-binding cassette (ABC) family of ATPases. The sequence homology within the carboxy-terminal domain is relatively high within the SMC1-SMC4 group, whereas SMC5 and SMC6 show some divergence in both of these sequences. In eukaryotic cells, the proteins are found as heterodimers of SMC1 paired with SMC3, SMC2 with SMC4, and SMC5 with SMC6 [].This entry represents the ATP-binding cassette domain of eukaryotic SMC3 proteins, which is found at the N terminus.
The structural maintenance of chromosomes (SMC) proteins are large (approximately 110 to 170kDa), and each is arranged into five recognizable domains. Amino-acid sequence homology of SMC proteins between species is largely confined to the amino- and carboxy-terminal globular domains. The amino-terminal domain contains a 'Walker A' nucleotide-binding domain (GxxGxGKS/T), which by mutational studies has been shown to be essential in several proteins. The carboxy-terminal domain contains a sequence (the DA-box) that resembles a 'Walker B' motif, and a motif with homology to the signature sequence of the ATP-binding cassette (ABC) family of ATPases. The sequence homology within the carboxy-terminal domain is relatively high within the SMC1-SMC4 group, whereas SMC5 and SMC6 show some divergence in both of these sequences. In eukaryotic cells, the proteins are found as heterodimers of SMC1 paired with SMC3, SMC2 with SMC4, and SMC5 with SMC6 [].This entry represents the ATP-binding cassette domain of eukaryotic SMC4 proteins.
This entry consists of the E3 SUMO-protein ligase Nse2 (also known as Mms21). Nse2 is an E3 SUMO-protein ligase component of the SMC5-SMC6 complex [, ]. Nse2 acts as an E3 ligase targeting several proteins for sumoylation and is required for efficient DNA repair and maintenance of genome stability [, , , ]. Nse2 and SMC5 may also be required for sister chromatid cohesion during prometaphase and mitotic progression; this role is apparently independent of SMC6 []. Nse2 is necessary for normal cell cycle progression in Arabidopsis, where Nse2 mutation results in abnormal root development [].
This entry represents the Nse3/MAGE () binding domain found in NSE4/EID family proteins [, ]. 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 [, , ]. 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 []. 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 []. 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 []and to the Nse3 (another SMC5-6 complex subunit) pocket [], which seems to increased the stability of the ATP-free SMC5/6 complex.
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 [, , ]. 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 []. 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 []. 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 []and to the Nse3 (another SMC5-6 complex subunit) pocket [], which seems to increased the stability of the ATP-free SMC5/6 complex.
