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

BMC Molecular and Cell Biology - Tập 21 - Trang 1-10 - 2020
András Horváth1, Gergely Rona2,3,4, Michele Pagano2,3,4, Philip W. Jordan1
1Biochemistry and Molecular Biology Department, Johns Hopkins University Bloomberg School of Public Health, Baltimore, USA
2Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, USA
3Perlmutter Cancer Center, New York University School of Medicine, New York, USA
4Howard Hughes Medical Institute, New York University School of Medicine, New York, USA

Tóm tắt

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. 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. 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.

Tài liệu tham khảo

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