Abstract
BackgroundThe 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.ResultsIn 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.ConclusionTaken 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.
Highlights
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
Much less research has been published about the SMC5/6 complex it is known to be involved in DNA damage repair and chromosome segregation during mitosis and meiosis [1, 5,6,7,8,9,10,11]
The focus of this study was the characterization of the interaction between NSMCE4A and G protein pathway suppressor 1 (GPS1)
Summary
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; it is known to be involved in homologous recombination repair (HRR) and chromosome segregation. Eukaryotes express three classes of structural maintenance of chromosome (SMC) complexes; cohesin, condensin and SMC5/6. Condensin complexes are best known for their role in chromatin condensation prior to chromosome segregation [4]. Much less research has been published about the SMC5/6 complex it is known to be involved in DNA damage repair and chromosome segregation during mitosis and meiosis [1, 5,6,7,8,9,10,11]
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