The CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells

Selective elimination of BRCA1-deficient cells by inhibitors of poly(ADP-ribose) polymerase (PARP) is a prime example of the concept of synthetic lethality in cancer therapy. This interaction is counteracted by the restoration of BRCA1-independent homologous recombination through loss of factors such as 53BP1, RIF1, and REV7/MAD2L2, which inhibit end resection of DNA double-strand breaks (DSBs). To identify additional factors involved in this process, we performed CRISPR/SpCas9-based loss-of-function screens and selected for factors that confer PARP inhibitor (PARPi) resistance in BRCA1-deficient cells. Loss of members of the CTC1-STN1-TEN1 (CST) complex were found to cause PARPi resistance in BRCA1-deficient cells in vitro and in vivo. We show that CTC1 depletion results in the restoration of end resection and that the CST complex may act downstream of 53BP1/RIF1. These data suggest that, in addition to its role in protecting telomeres, the CST complex also contributes to protecting DSBs from end resection. Using CRISPR/SpCas9-based loss-of-function screens, Barazas et al. show that loss of the CTC1-STN1-TEN1 (CST) complex promotes PARP inhibitor resistance in BRCA1-deficient cells. Mechanistically, the CST complex maintains double-strand break end stability in addition to its role in protecting telomeric ends

Toekomst van de Nederlandse detailhandelsstructuur: Een verkenning van drijvende krachten

De Nederlandse detailhandelsstructuur wordt bepaald door een samenspel van de markt, de ruimte en de regels. Uitspraken over de toekomst van deze structuur kunnen gedaan worden door veranderingen in dit krachtenveld goed in te schatten. Zo is het relevant te weten hoe retailers inspelen op het fenomeen internet, maar ook hoe beleggers, gemeenten en ontwikkelaars omgaan met bouwen en vernieuwen van winl<elgebieden. Dynamiek kan ook komen vanuit een verandering in regelgeving, bijvoorbeeld Europese mededingingsregels die de Nederlandse restricties onder druk kunnen zetten.Real Estate and HousingArchitectur

De conditie en de minerale - voedingstoestand van opstanden van groveden (Pinus sylvestris) en Corsicaanse den (Pinus nigra var. maritima) in de Peel en op de Zuidoostelijke Veluwe

Onderzoek naar de samenhang tussen het optreden van scheut- en kroonsterfte in opstanden van groveden en Corsicaanse den, de minerale voedingstoestand en het verhoogde optreden van chemische "stress" indicatoren in de hormonenbalan

De conditie en de minerale - voedingstoestand van opstanden van groveden (Pinus sylvestris) en Corsicaanse den (Pinus nigra var. maritima) in de Peel en op de Zuidoostelijke Veluwe

Onderzoek naar de samenhang tussen het optreden van scheut- en kroonsterfte in opstanden van groveden en Corsicaanse den, de minerale voedingstoestand en het verhoogde optreden van chemische "stress" indicatoren in de hormonenbalan

High-rate silicon nitride deposition for photovoltaics : from fundamentals to industrial application

The development of a novel plasma technique for high rate (> 1 nm/s) silicon nitride deposition for multifunctional antireflection coatings on crystalline silicon solar cells is described. The research has involved the analysis of the structural and optical properties of the silicon nitride films as obtained under different operating conditions using the N2-SiH4 and NH3-SiH4 reactant mixture. Furthermore, the fundamental plasma processes and the film growth mechanism have been studied in terms of plasma chemistry, plasma species, and their contribution to film growth. The feasibility of the application of the high-rate deposited silicon nitride as a bulk passivating antireflection coating has been proven by lab-scale experiments on multicrystalline silicon solar cells and the successful transfer of the technique into an industrial inline deposition system for high-volume production of solar cells is reported