The identification of a novel role for BRCA1 in regulating RNA Polymerase I transcription

The unrestrained proliferation of cancer cells requires a high level of ribosome biogenesis. The first stage of ribosome biogenesis is the transcription of the large ribosomal RNAs (rRNAs); the structural and functional components of the ribosome. Transcription of rRNA is carried out by RNA polymerase I (Pol-I) and its associated holoenzyme complex. Here we report that BRCA1, a nuclear phosphoprotein, and a known tumour suppressor involved in variety of cellular processes such as DNA damage response, transcriptional regulation, cell cycle control and ubiquitylation, is associated with rDNA repeats, in particular with the regulatory regions of the rRNA gene. We demonstrate that BRCA1 interacts directly with the basal Pol-I transcription factors; upstream binding factor (UBF), selectivity factor-1 (SL1) as well as interacting with RNA Pol-I itself. We show that in response to DNA damage, BRCA1 occupancy at the rDNA repeat is decreased and the observed BRCA1 interactions with the Pol-I transcription machinery are weakened. We propose, therefore, that there is a rDNA associated fraction of BRCA1 involved in DNA damage dependent regulation of Pol-I transcription, regulating the stability and formation of the Pol-I holoenzyme during initiation and/or elongation in response to DNA damage

CPDW Project. Assessment of Cytotoxicological Potential of Products in Contact with Drinking Water.

The investigations described in this report were conducted as part of the European Project "Development of Harmonised tests to be used in the European Approval Scheme (EAS) concerning Construction Products in contact with Drinking Water (CPDW)", under Contract no. EVK1-CT2000-00052. This project is financially supported by the European Commission, the national authorities of Denmark, France, Germany, Portugal and the United Kingdom and the material suppliers in these countries and Europe, respectively. Work Package 2 concerned the cytotoxicity properties of materials of this project. The institutes participating in the investigations and discussions in this work package are listed below.JRC.DDG.H-Institute for environment and sustainability (Ispra

Upstream-binding factor is sequestered into herpes simplex virus type 1 replication compartments

Previous reports have shown that adenovirus recruits nucleolar protein upstream-binding factor (UBF) into adenovirus DNA replication centres. Here, we report that despite having a different mode of viral DNA replication, herpes simplex virus type 1 (HSV-1) also recruits UBF into viral DNA replication centres. Moreover, as with adenovirus, enhanced green fluorescent protein-tagged fusion proteins of UBF inhibit viral DNA replication. We propose that UBF is recruited to the replication compartments to aid replication of HSV-1 DNA. In addition, this is a further example of the role of nucleolar components in viral life cycle

Disposable electrochromic polyaniline sensor based on a redox response using a conventional camera: A first approach to handheld analysis

We present a disposable optical sensor for Ascorbic Acid (AA). It uses a polyaniline based electrochromic sensing film that undergoes a color change when exposed to solutions of ascorbic acid at pH 3.0. The color is monitored by a conventional digital camera working with the hue (H) color coordinate. The electrochromic film was deposited on an Indium Tin Oxide (ITO) electrode by cyclic voltammetry and then characterized by atomic force microscopy, electrochemical and spectroscopic techniques. An estimation of the initial rate of H, as ΔH/Δt, is used as the analytical parameter and resulted in the following logarithmic relationship: ΔH/Δt = 0.029 log[AA] + 0.14, with a limit of detection of 17 μM. The relative standard deviation when using the same membrane 5 times was 7.4% for the blank, and 2.6% (for n = 3) on exposure to ascorbic acid in 160 μM concentration. The sensor is disposable and its applicability to pharmaceutical analysis was demonstrated. This configuration can be extended for future handheld configurations.We acknowledge financial support from the Junta de Andalucía (Proyecto de Excelencia P10-FQM-5974) and from the Ministerio de Economía y Competitividad (CTQ2013-44545-R). These projects were partially supported by European Regional Development Funds (ERDF)

Spinnability and characteristics of polyvinylidene fluoride (PVDF)-based bicomponent fibers with a carbon nanotube (CNT) modified polypropylene core for piezoelectric applications

Biodiesel production has received considerable attention in the recent past as a nonpolluting fuel. However, this assertion has been based on its biodegradability and reduction in exhaust emissions. Assessments of water and soil biodiesel pollution are still limited. Spill simulation with biodiesel and their diesel blends in soils were carried out, aiming at analyzing their cytotoxic and genotoxic potentials. While the cytotoxicity observed may be related to diesel contaminants, the genotoxic and mutagenic effects can be ascribed to biodiesel pollutants. Thus, taking into account that our data stressed harmful effects on organisms exposed to biodiesel-polluted soils, the designation of this biofuel as an environmental-friendly fuel should be carefully reviewed to assure environmental quality. (C) 2011 Elsevier B.V. All rights reserved

Anthropogenic organic micro-pollutants and pathogens in the urban water cycle: assessment, barriers and risk communication (ASKURIS)

In urban areas, water often flows along a partially closed water cycle in which treated municipal wastewater is discharged into surface waters which are one source of raw waters used for drinking water supply. A number of organic micro-pollutants (OMP) can be found in different water compartments. In the near future, climatic and demographic changes will probably contribute to an increase of OMP and antibiotic-resistant pathogens in aquatic ecosystems. The occurrence of OMP, possible adverse effects on aquatic organisms and human health and the public perception must be carefully assessed to properly manage and communicate potentially associated risks and to implement appropriate advanced treatment options at the optimum location within the water cycle. Therefore, the interdisciplinary research project ASKURIS focuses on identification and quantification, toxicological assessment and removal of organic micro-pollutants and antibiotic-resistant pathogens in the Berlin water cycle, life cycle-based economic and environmental assessment, public perception and management of potential risks

Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation