Breaks in double stranded DNA often arise during DNA replication or as a result of exposure to DNA-damaging agents. Quick and accurate repair of these breaks is crucial for cell survival and genomic stability. Structural maintenance of chromosomes (SMC) family members form heterodimeric complexes that modulate sister chromatid cohesion and chromosome condensation during mitosis. SMC5 and SMC6 play a crucial role in DNA repair as they form a complex with six conserved nonSMC subunits, including a ubiquitin E3 ligase NSE1 and a SUMO ligase NSE2. Specifically, this complex is crucial for sister chromatid homologous recombination DNA repair and also for prevention of chromosomal rearrangements. The NSE1 protein contains a RING-like motif that promotes DNA repair functions of the SMC5/SMC6 complex and full deletion of NSE1 is lethal to cells. NSE2 stimulates sumoylation of SMC6 and the DNA repair protein TRAX. Depletion of the NSE2 protein by RNA interference leaves the cell vulnerable to DNA damage-induced apoptosis.
Function:
Component of the SMC5-SMC6 complex, a complex involved in 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 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). Has in vitro ubiquitin ligase activity in presence of NDNL2. Is involved in positive regulation of response to DNA damage stimulus.
Subunit:
Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NDNL2. NSMCE1, NSMCE4A or EID3 and NDNL2 probably form a subcomplex that bridges the head domains of the SMC5:SMC6 heterodimer.
Subcellular Location:
Nucleus. Chromosome, telomere
Post-translational modifications:
Ubiquitinated.
Similarity:
Belongs to the NSE1 family.
Contains 1 NSE1-type zinc finger.
SWISS:
Q8WV22
Gene ID:
197370
Database links:
Entrez Gene: 197370 Human
Entrez Gene: 67711 Mouse
Entrez Gene: 361645 Rat
SwissProt: Q8WV22 Human
SwissProt: Q9D720 Mouse
SwissProt: Q499U6 Rat
Unigene: 284295 Human
Unigene: 4467 Mouse
Unigene: 17063 Rat
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