Topoisomerase IIα (TOP2α) is essential for chromosomal condensation and segregation, as well as genomic integrity. Here we report that RNF168, an E3 ligase mutated in the human RIDDLE syndrome, interacts with TOP2α and mediates its ubiquitylation. RNF168 deficiency impairs decatenation activity of TOP2α and promotes mitotic abnormalities and defective chromosomal segregation. Our data also indicate that RNF168 deficiency, including in human breast cancer cell lines, confers resistance to the anti-cancer drug and TOP2 inhibitor etoposide. We also identify USP10 as a deubiquitylase that negatively regulates TOP2α ubiquitylation and restrains its chromatin association. These findings provide a mechanistic link between the RNF168/USP10 axis and TOP2α ubiquitylation and function, and suggest a role for RNF168 in the response to anti-cancer chemotherapeutics that target TOP2.

In this paper, a 4-port multi-input multi-output (MIMO) antenna based on substrate integrated gap wave guide (SIGW) is presented for down-link satellite applications. The proposed MIMO antenna consists of four rectangular-shaped radiating slots, which are fed via SIGW to minimize dispersion and insertion loss. Firstly, single antenna element (reference antenna) is designed to have impedance matching and stable radiation pattern over the bandwidth 13.4-13.65 GHz. Afterward, different antenna configurations are studied to combine four identical elements of the reference one for the sake of minimizing mutual coupling between them. In this work, the edge-to-edge separation between the antenna elements for orthogonal and opposite orientations are 9.3mm and 17.3mm, respectively. The mutual coupling between antenna elements is suppressed by etching the upper ground in the region between the antenna elements. Moreover, further optimization is carried out by changing the dimensions of the etched slot to reach higher isolation between radiating slots for better MIMO diversity performance. With this approach, the realized gain is increased by 3-dBi and the maximum mutual coupling achieved at 13.5 GHz between port (1,2) and port (1,3) are -63 dB and -78 dB, respectively with isolation enhancement of 38 dB between port (1,2) and 48 dB between port (1,3). Both simulated and measured results indicate that the proposed antenna has a bandwidth of 13.3-13.8 GHz, with a high isolation greater than 40 dB. Furthermore, the realized antenna gain is around 9-dBi with radiation efficiency of 86%. In addition, the designed MIMO antenna offers excellent radiation characteristics and stable gain over the whole operating band. To explore the diversity of the MIMO system the envelope correlation coefficient (ECC), multiplexing efficiency (ME), diversity gain (DG), channel capacity loss (CCL) and total active reflection coefficient (TARC) are studied. Finally, good consistency between simulation and measured outcomes is obtained confirming the validity of the MIMO antenna for real life satellite application systems.INDEX TERMS MIMO antenna, SIGW, satellite downlink applications.