Interaction between NSMCE4A and GPS1 links the SMC5/6 complex to the COP9 signalosome

BMC Mol Cell Biol. 2020 May 8;21(1):36. doi: 10.1186/s12860-020-00278-x.


Background: The SMC5/6 complex, cohesin and condensin are the three mammalian members of the structural maintenance of chromosomes (SMC) family, large ring-like protein complexes that are essential for genome maintenance. The SMC5/6 complex is the least characterized complex in mammals; however, it is known to be involved in homologous recombination repair (HRR) and chromosome segregation.

Results: In this study, a yeast two-hybrid screen was used to help elucidate novel interactions of the kleisin subunit of the SMC5/6 complex, NSMCE4A. This approach discovered an interaction between NSMCE4A and GPS1, a COP9 signalosome (CSN) component, and this interaction was further confirmed by co-immunoprecipitation. Additionally, GPS1 and components of SMC5/6 complex colocalize during interphase and mitosis. CSN is a cullin deNEDDylase and is an important factor for HRR. Depletion of GPS1, which has been shown to negatively impact DNA end resection during HRR, caused an increase in SMC5/6 levels at sites of laser-induced DNA damage. Furthermore, inhibition of the dennedylation function of CSN increased SMC5/6 levels at sites of laser-induced DNA damage.

Conclusion: Taken together, these data demonstrate for the first time that the SMC5/6 and CSN complexes interact and provides evidence that the CSN complex influences SMC5/6 functions during cell cycle progression and response to DNA damage.

Keywords: COP9 signalosome; DNA repair; Deneddylation; GPS1; NSMCE4A; SMC5/6.

MeSH terms

  • COP9 Signalosome Complex / antagonists & inhibitors
  • COP9 Signalosome Complex / genetics
  • COP9 Signalosome Complex / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cytoplasm / metabolism
  • DNA Damage / genetics
  • DNA Damage / radiation effects
  • DNA Repair
  • Humans
  • Interphase / genetics
  • Mitosis / genetics
  • Protein Processing, Post-Translational
  • RNA, Small Interfering
  • Two-Hybrid System Techniques


  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • RNA, Small Interfering
  • SMC5 protein, human
  • SMC6 protein, human
  • COP9 Signalosome Complex