Biology subjects

Hurst, V.

Publications and source records attributed to Hurst, V..

3 recordsLinked to original sources

bioRxiv2020

Uncoordinated long-patch base excision repair at juxtaposed DNA lesions generates a lethal accumulation of double-strand breaks

Inhibition of the TOR pathway (TORC2, or Ypk1/2), or the depolymerization of actin filaments results in catastrophic fragmentation of the yeast genome upon exposure to low doses of the radiomimetic drug Zeocin. We find that the accumulation of double-strand breaks (DSB) is not due to altered DSB repair, but by the uncoordinated activity of base excision repair (BER) at Zeocin-modified DNA bases. We inhibit DSB formation by eliminating glycosylases and/or the endonucleases Apn1/2 and Rad1, implicating these conserved BER enzymes, or events downstream of them, in the conversion of base damage into DSBs. Among DNA polymerases, the reduction of Pol {delta}, and to a lesser extent Pol {varepsilon} and Trf4 (a Pol {beta}-like polymerase), reduces DSB formation. Finally, the BER enzymes, Ogg1 and AP endonuclease, are shown to co-precipitate with actin from yeast extracts and as purified proteins, suggesting that actin may interfere directly with the repair of Zeocin-induced damage.

molecular biology↗

bioRxiv2019

The ARRIVE guidelines 2019: updated guidelines for reporting animal research

Reproducible science requires transparent reporting. The ARRIVE guidelines were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved.\n\nHere we introduce ARRIVE 2019. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise the items and split the guidelines into two sets, the ARRIVE Essential 10, which constitute the minimum requirement, and the Recommended Set, which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers to verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document that serves 1) to explain the rationale behind each item in the guidelines, 2) to clarify key concepts and 3) to provide illustrative examples. We aim through these changes to help ensure that researchers, reviewers and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

scientific communication and education↗

bioRxiv2019

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments.\n\nDespite widespread endorsement by the scientific community, the impact of the ARRIVE guidelines on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This Explanation and Elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2019, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature.

scientific communication and education↗