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.

中文翻译：

---

NSMCE4A和GPS1之间的相互作用将SMC5 / 6复合体连接到COP9信号小体。

背景技术SMC5 / 6复合物，粘着素和凝缩蛋白是染色体结构维持（SMC）家族的三个哺乳动物成员，SMC是大的环状蛋白复合物，对基因组的维持至关重要。SMC5 / 6复合物是哺乳动物中特征最少的复合物。然而，已知它参与同源重组修复（HRR）和染色体分离。结果在这项研究中，使用酵母双杂交筛选来帮助阐明SMC5 / 6复合物NSMCE4A的kleisin亚基的新型相互作用。这种方法发现了NSMCE4A与GPS1（COP9信号小体（CSN）组件）之间的相互作用，并且通过共免疫沉淀进一步证实了这种相互作用。此外，GPS1和SMC5 / 6复合体的组件在相间和有丝分裂期间共定位。CSN是cullin的去NEDDylase，是HRR的重要因素。已显示GPS1的消耗对HRR期间的DNA末端切除有负面影响，导致激光诱导的DNA损伤部位的SMC5 / 6水平升高。此外，抑制CSN的树突化功能会增加激光诱导的DNA损伤部位的SMC5 / 6水平。结论综上所述，这些数据首次证明SMC5 / 6和CSN复合物相互作用，并提供证据表明CSN复合物在细胞周期进程和对DNA损伤的反应过程中影响SMC5 / 6功能。抑制CSN的树突化功能会增加激光诱导的DNA损伤部位的SMC5 / 6水平。结论综上所述，这些数据首次证明SMC5 / 6和CSN复合物相互作用，并提供证据表明CSN复合物在细胞周期进程和对DNA损伤的反应过程中影响SMC5 / 6功能。抑制CSN的树突化功能会增加激光诱导的DNA损伤部位的SMC5 / 6水平。结论综上所述，这些数据首次证明SMC5 / 6和CSN复合物相互作用，并提供证据表明CSN复合物在细胞周期进程和对DNA损伤的反应过程中影响SMC5 / 6功能。