Next Article in Journal
Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis
Previous Article in Journal
The Impact of Vitamin E and Other Fat-Soluble Vitamins on Alzheimer´s Disease
Article

Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress

1
Center for Reproductive Medicine, Amsterdam Research Institute Reproduction and Development, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
2
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
3
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
4
Mass Spectrometry of Biomacromolecules, Swammerdam Institute for Life Sciences, University of Amsterdam, 1090 GE Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Guillermo T. Sáez
Int. J. Mol. Sci. 2016, 17(11), 1782; https://doi.org/10.3390/ijms17111782
Received: 8 July 2016 / Revised: 14 September 2016 / Accepted: 20 October 2016 / Published: 26 October 2016
(This article belongs to the Section Biochemistry)
The 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
Keywords: Structural Maintenance of Chromosomes 5/6 complex (SMC5/6); Non-SMC Element 2 (NSMCE2); Topoisomerase II α (TOP2A); DNA double-strand breaks (DSBs); Ionizing Radiation (IR); CRISPR-Cas9 Structural Maintenance of Chromosomes 5/6 complex (SMC5/6); Non-SMC Element 2 (NSMCE2); Topoisomerase II α (TOP2A); DNA double-strand breaks (DSBs); Ionizing Radiation (IR); CRISPR-Cas9
Show Figures

Graphical abstract

MDPI and ACS Style

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. https://doi.org/10.3390/ijms17111782

AMA Style

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. https://doi.org/10.3390/ijms17111782

Chicago/Turabian Style

Verver, Dideke E., Yi Zheng, Dave Speijer, Ron Hoebe, Henk L. Dekker, Sjoerd Repping, Jan Stap, and Geert Hamer. 2016. "Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress" International Journal of Molecular Sciences 17, no. 11: 1782. https://doi.org/10.3390/ijms17111782

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop