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  • Given the widespread occurrence of oncogene induced RS and

    2019-09-11

    Given the widespread occurrence of oncogene-induced RS and the increasing clinical interest in small molecule inhibitors that further exacerbate RS in human cancers (such as ATR inhibitors), our findings point to a protective role for RAD52 in the maintenance of cancer cell viability. As such, RAD52 could be a plausible target for therapies targeted at tumors with excessive RS and/or those exposed to agents that generate additional RS, such as ATRi. Furthermore, RAD52 inhibition might be selective, given the apparently limited role of RAD52 in genome maintenance in normal Physcion (Feng et al., 2011, Lok et al., 2013, Lok and Powell, 2012, Rijkers et al., 1998). Of possible relevance to this, abrogation of RAD52 function leads to increased cell death in lung tumors and in BRCA2-deficient cancer cells (Feng et al., 2011, Lok et al., 2013). We propose that this could be due to the abrogation of MiDAS, which is required to sustain viability in these cells. Additionally, amplification of the 12p13.33 locus comprising the RAD52 gene is associated with the development of squamous cell carcinomas of the lung (Lieberman et al., 2016). Hence, we propose that the treatment of patients with MiDAS inhibitors, in combination with agents such as ATR inhibitors, might synergistically and selectively target tumors exhibiting oncogene-activated RS. Sotiriou et al. (2016) report in this issue of Molecular Cell that RAD52 is required for the BIR-mediated repair of collapsed DNA replication forks in response to oncogene-induced replication stress. Their data are fully consistent with ours.
    Experimental Procedures
    Author Contributions
    Acknowledgments We thank Dr. Claudia Lukas, Dr. Jiri Lukas, and members of the I.D.H. laboratory for useful discussions and Hocine Mankouri and Ying Liu for critical reading of the manuscript. We also thank Thanos Halazonetis for sharing data prior to submission. Work in the authors’ laboratory is funded by the Danish National Research Foundation (DNRF115), The European Research Council (ERC Project Number 321717), and The Nordea Foundation. R.B. and S.M. were recipients of Danish Medical Research Council fellowships (DFF-4004-00155B, DFF-6110-00169B, and DFF-6110-00243B).
    Introduction In order to reduce the enormous utilization of fossil fuels and other related environmental issues existing in our day-to-day life activities, scientific community has been taking efforts to develop eco-friendly energy storage devices with high energy and power density ratings, ultra-fast charge/discharge capacity, long cycle life and lower maintenance costs [1], [2], [3], [4]. Among the presently available energy storage devices, supercapacitors have acquired a tremendous interest, because of their remarkable characteristics such as higher power density than batteries and higher energy density than traditional capacitors in their device performance [5], [6], [7], [8], [9]. These advantages are essential for their real time applications in all portable electronic devices, electric vehicles, instant switches, back-up power supply, motor starter, industrial power and energy management, etc. [10]. Based on the energy storage mechanism, supercapacitor electrode materials may be classified into two types: (i) Pseudocapacitors and (ii) Electrochemical double layer capacitors (EDLC\'s). Pseudocapacitor electrodes employ redox reaction mechanism for charge storage and are generally based on metal oxides and conducting polymers, whereas, electrochemical double layer capacitors store charges through an accumulation of electrostatic charges at the electrode/electrolyte interface and involve typically carbonaceous materials having appreciably high specific surface area [11], [12], [13]. Due to the multiple oxidation states of pseudocapacitor electrode materials, they tend to deliver higher specific capacitance and energy density values than that of EDLC electrode materials [14].