RNase H activities counteract a toxic effect of Polymerase in cells replicating with depleted dNTP pools

RNA:DNA hybrids are transient physiological intermediates that arise during several cellular processes such as DNA replication. In pathological situations, they may stably accumulate and pose a threat to genome integrity. Cellular RNase H activities process these structures to restore the correct DNA:DNA sequence. Yeast cells lacking RNase H are negatively affected by depletion of deoxyribonucleotide pools necessary for DNA replication. Here we show that the translesion synthesis DNA polymerase (Pol ) plays a role in DNA replication under low deoxyribonucleotides condition triggered by hydroxyurea. In particular, the catalytic reaction performed by Pol is detrimental for RNase H deficient cells, causing DNA damage checkpoint activation and G2/M arrest. Moreover, a Pol mutant allele with enhanced ribonucleotide incorporation further exacerbates the sensitivity to hydroxyurea of cells lacking RNase H activities. Our data are compatible with a model in which Pol activity facilitates the formation or stabilization of RNA:DNA hybrids at stalled replication forks. However, in a scenario where RNase H activity fails to restore DNA, these hybrids become highly toxic for cells

Large community-acquired Legionnaires’ disease outbreak caused by Legionella pneumophila serogroup 1, Italy, July to August 2018

In July 2018, a large outbreak of Legionnaires\u2019 disease (LD) caused by Legionella pneumophila serogroup 1 (Lp1) occurred in Bresso, Italy. Fifty-two cases were diagnosed, including five deaths. We performed an epidemiological investigation and prepared a map of the places cases visited during the incubation period. All sites identified as potential sources were investigated and sampled. Association between heavy rainfall and LD cases was evaluated in a case-crossover study. We also performed a case\u2013control study and an aerosol dispersion investigation model. Lp1 was isolated from 22 of 598 analysed water samples; four clinical isolates were typed using monoclonal antibodies and sequence-based typing. Four Lp1 human strains were ST23, of which two were Philadelphia and two were France-Allentown subgroup. Lp1 ST23 France-Allentown was isolated only from a public fountain. In the case-crossover study, extreme precipitation 5\u20136 days before symptom onset was associated with increased LD risk. The aerosol dispersion model showed that the fountain matched the case distribution best. The case\u2013control study demonstrated a significant eightfold increase in risk for cases residing near the public fountain. The three studies and the matching of clinical and environmental Lp1 strains identified the fountain as the source responsible for the epidemic

Photoinduced transformation of waste-derived soluble bio-based substances

[EN] Waste-derived, soluble bin-based substances (SBO), are effective low-cost photosensitizers that could find application in pollutant photodegradation. For this reason, it is important to understand if and to what extent irradiation could modify their properties. The exposure of SBO to simulated sunlight induced important spectral and structural modifications. Both the whole material and its acid-soluble fraction were characterized, highlighting several properties in common with humic and fulvic substances, including absorption spectra, specific absorbance and fluorescence behavior. The latter was described with a three-component model using PARAFAC analysis. Irradiation induced SBO photobleaching, but the absorbance of the acid-soluble fraction increased with irradiation. This finding suggests a progressive photochemical solubilization of SBO, which is confirmed by the increase of the carboxylic groups. In addition to absorbance, the fluorescence of whole SBO was also decreased by irradiation, thereby suggesting that both chromophores and fluorophores were photodegraded. The increasingly hydrophilic character given to SBO by irradiation also accounted for the photoinduced decrease of the surfactant properties of the material. (C) 2015 Elsevier B.V. All rights reserved.This work was funded by the 7thFP IRSES-2010-269128-EnvironBos Marie Curie Action and by Ministero delle Politiche Agricole e Forestali (Agrienergia project). The authors are grateful to the following private and/or public Italian institutions: (a) Acea Pinerolese Spa in Pinerolo (TO) for supplying the SBO sourcing materials; (b) Studio Chiono ed Associati in Rivarolo Canavese (TO) for making available pilot equipment and services for the production of the SBO.Avetta, P.; Berto, S.; Bianco Prevot, A.; Minella, M.; Montoneri, E.; Persico, D.; Vione, D.... (2015). Photoinduced transformation of waste-derived soluble bio-based substances. Chemical Engineering Journal. 274:247-255. https://doi.org/10.1016/j.cej.2015.03.126S24725527

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio

Transcription reinitiation by RNA polymerase III

The retention of transcription proteins at an actively transcribed gene contributes to maintenance of the active transcriptional state and increases the rate of subsequent transcription cycles relative to the initial cycle. This process, called transcription reinitiation, generates the abundant RNAs in living cells. The persistence of stable preinitiation intermediates on activated genes representing at least a subset of basal transcription components has long been recognized as a shared feature of RNA polymerase (Pol) I, II and III-dependent transcription in eukaryotes. Studies of the Pol III transcription machinery and its target genes in eukaryotic genomes over the last fifteen years, has uncovered multiple details on transcription reinitiation. In addition to the basal transcription factors that recruit the polymerase, Pol III itself can be retained on the same gene through multiple transcription cycles by a facilitated recycling pathway. The molecular bases for facilitated recycling are progressively being revealed with advances in structural and functional studies. At the same time, progress in our understanding of Pol III transcriptional regulation in response to different environmental cues points to the specific mechanism of Pol III reinitiation as a key target of signaling pathway regulation of cell growth. This article is part of a Special Issue entitled: Transcription by Odd Pols