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

András Horváth, Gergely Rona, Michele Pagano, Philip W. Jordan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number36
JournalBMC Molecular and Cell Biology
Volume21
Issue number1
DOIs
StatePublished - May 8 2020

Keywords

  • COP9 signalosome
  • DNA repair
  • Deneddylation
  • GPS1
  • NSMCE4A
  • SMC5/6

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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