110 research outputs found

    The RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader involved in the response to DNA damage.

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    Site-specific histone ubiquitylation plays a central role in orchestrating the response to DNA double-strand breaks (DSBs). DSBs elicit a cascade of events controlled by the ubiquitin ligase RNF168, which promotes the accumulation of repair factors such as 53BP1 and BRCA1 on the chromatin flanking the break site. RNF168 also promotes its own accumulation, and that of its paralog RNF169, but how they recognize ubiquitylated chromatin is unknown. Using methyl-TROSY solution NMR spectroscopy and molecular dynamics simulations, we present an atomic resolution model of human RNF169 binding to a ubiquitylated nucleosome, and validate it by electron cryomicroscopy. We establish that RNF169 binds to ubiquitylated H2A-Lys13/Lys15 in a manner that involves its canonical ubiquitin-binding helix and a pair of arginine-rich motifs that interact with the nucleosome acidic patch. This three-pronged interaction mechanism is distinct from that by which 53BP1 binds to ubiquitylated H2A-Lys15 highlighting the diversity in site-specific recognition of ubiquitylated nucleosomes

    A Novel 5-Enolpyruvylshikimate-3-Phosphate Synthase Shows High Glyphosate Tolerance in Escherichia coli and Tobacco Plants

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    A key enzyme in the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the primary target of the broad-spectrum herbicide glyphosate. Identification of new aroA genes coding for EPSPS with a high level of glyphosate tolerance is essential for the development of glyphosate-tolerant crops. In the present study, the glyphosate tolerance of five bacterial aroA genes was evaluated in the E. coli aroA-defective strain ER2799 and in transgenic tobacco plants. All five aroA genes could complement the aroA-defective strain ER2799, and AM79 aroA showed the highest glyphosate tolerance. Although glyphosate treatment inhibited the growth of both WT and transgenic tobacco plants, transgenic plants expressing AM79 aroA tolerated higher concentration of glyphosate and had a higher fresh weight and survival rate than plants expressing other aroA genes. When treated with high concentration of glyphosate, lower shikimate content was detected in the leaves of transgenic plants expressing AM79 aroA than transgenic plants expressing other aroA genes. These results suggest that AM79 aroA could be a good candidate for the development of transgenic glyphosate-tolerant crops

    Interaction-enhanced and time-aware graph convolutional network for successive point-of-interest recommendation in traveling enterprises

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    Abstract Extensive user check-in data incorporating user preferences for location is collected through Internet of Things (IoT) devices, including cell phones and other sensing devices in location-based social network. It can help traveling enterprises intelligently predict users’ interests and preferences, provide them with scientific tourism paths, and increase the enterprises income. Thus, successive point-of-interest (POI) recommendation has become a hot research topic in augmented Intelligence of Things (AIoT). Presently, various methods have been applied to successive POI recommendations. Among them, the recurrent neural network-based approaches are committed to mining the sequence relationship between POIs, but ignore the high-order relationship between users and POIs. The graph neural network-based methods can capture the high-order connectivity, but it does not take the dynamic timeliness of POIs into account. Therefore, we propose an I nteraction-enhanced and T ime-aware G raph C onvolution N etwork (ITGCN) for successive POI recommendation. Specifically, we design an improved graph convolution network for learning the dynamic representation of users and POIs. We also designed a self-attention aggregator to embed high-order connectivity into the node representation selectively. The enterprise management systems can predict the preferences of users, which is helpful for future planning and development. Finally, experimental results prove that ITGCN brings better results compared to the existing methods
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