Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress
AbstractThe structural maintenance of chromosomes (SMC) protein complexes shape and regulate the structure and dynamics of chromatin, thereby controlling many chromosome-based processes such as cell cycle progression, differentiation, gene transcription and DNA repair. The SMC5/6 complex is previously described to promote DNA double-strand breaks (DSBs) repair by sister chromatid recombination, and found to be essential for resolving recombination intermediates during meiotic recombination. Moreover, in budding yeast, SMC5/6 provides structural organization and topological stress relief during replication in mitotically dividing cells. Despite the essential nature of the SMC5/6 complex, the versatile mechanisms by which SMC5/6 functions and its molecular regulation in mammalian cells remain poorly understood. By using a human osteosarcoma cell line (U2OS), we show that after the CRISPR-Cas9-mediated removal of the SMC5/6 subunit NSMCE2, treatment with the topoisomerase II inhibitor etoposide triggered an increased sensitivity in cells lacking NSMCE2. In contrast, NSMCE2 appeared not essential for a proper DNA damage response or cell survival after DSB induction by ionizing irradiation (IR). Interestingly, by way of immunoprecipitations (IPs) and mass spectrometry, we found that the SMC5/6 complex physically interacts with the DNA topoisomerase II α (TOP2A). We therefore propose that the SMC5/6 complex functions in resolving TOP2A-mediated DSB-repair intermediates generated during replication. View Full-Text
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Verver, D.E.; Zheng, Y.; Speijer, D.; Hoebe, R.; Dekker, H.L.; Repping, S.; Stap, J.; Hamer, G. Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress. Int. J. Mol. Sci. 2016, 17, 1782.
Verver DE, Zheng Y, Speijer D, Hoebe R, Dekker HL, Repping S, Stap J, Hamer G. Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress. International Journal of Molecular Sciences. 2016; 17(11):1782.Chicago/Turabian Style
Verver, Dideke E.; Zheng, Yi; Speijer, Dave; Hoebe, Ron; Dekker, Henk L.; Repping, Sjoerd; Stap, Jan; Hamer, Geert. 2016. "Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress." Int. J. Mol. Sci. 17, no. 11: 1782.
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