Oxidative DNA damage is instrumental in hyperreplication stress-induced inviability of Escherichia coli

En Escherichia coli, un aumento en la forma unida de ATP del iniciador de proteína DnaA da resultados en hiperiniciación e inviabilidad. Aquí, mostramos que dicha replicación de estrés es tolerada en el crecimiento anaeróbico. En las células de hiperiniciación, un cambio de la anaeróbica para crecimiento aeróbico dio como resultado la fragmentación aparente de cromosomas y una disminución en su concentración terminal, lo que conduce a un aumento dramático de la ratio ori/ter y el cese del crecimiento celular. La viabilidad aeróbica fue restaurada por reducir el nivel de especies reactivas del oxígeno (ROS) o por eliminación mutM (Fpg glicosilasa). Las roturas de la doble hélice observadas en las células de hiperiniciación resultan, por lo tanto, del encuentro entre los tenedores de replicación y las lesiones de ADN de una sola hélice generadas mientras se quitan bases oxidadas, principalmente 8-oxoG, a partir del ADN. Llegamos a la conclusión de que existe un delicado equilibrio entre la replicación cromosómica y el daño del ADN infligido a ROS por lo que el número de horquillas de replicación sólo puede aumentar cuando la formación de ROS se reduce o si la reparación pertinente se ve comprometida.In Escherichia coli, an increase in the ATP bound form of the DnaA initiator protein results in hyperinitiation and inviability. Here, we show that such replication stress is tolerated during anaerobic growth. In hyperinitiating cells, a shift from anaerobic to aerobic growth resulted in appearance of fragmented chromosomes and a decrease in terminus concentration, leading to a dramatic increase in ori/ter ratio and cessation of cell growth. Aerobic viability was restored by reducing the level of reactive oxygen species (ROS) or by deleting mut M (Fpg glycosylase). The double-strand breaks observed in hyperinitiating cells therefore results from replication forks encountering single-stranded DNA lesions generated while removing oxidized bases, primarily 8-oxoG, from the DNA. We conclude that there is a delicate balance between chromosome replication and ROS inflicted DNA damage so the number of replication forks can only increase when ROS formation is reduced or when the pertinent repair is compromised.-- Unión Europea (PIRG05-GA-2009-247241) -- Danish Research Concil for Natural Sciences (09-064250/FNU) -- Lundbeck Foundation -- Novo Nordist Foundation -- University of Copenhagen para presenter por open accesspeerReviewe

Fast resolution change in neutral helium atom microscopy

In neutral helium atom microscopy, a beam of atoms is scanned across a surface. Though still in its infancy, neutral helium microscopy has seen a rapid development over the last few years. The inertness and low energy of the helium atoms (less than 0.1 eV) combined with a very large depth of field and the fact that the helium atoms do not penetrate any solid material at low energies open the possibility for a non-destructive instrument that can measure topology on the nanoscale even on fragile and insulating surfaces. The resolution is determined by the beam spot size on the sample. Fast resolution change is an attractive property of a microscope because it allows different aspects of a sample to be investigated and makes it easier to identify specific features. However up till now it has not been possible to change the resolution of a helium microscope without breaking the vacuum and changing parts of the atom source. Here we present a modified source design, which allows fast, step wise resolution change. The basic design idea is to insert a moveable holder with a series of collimating apertures in front of the source, thus changing the effective source size of the beam and thereby the spot size on the surface and thus the microscope resolution. We demonstrate a design with 3 resolution steps. The number of resolution steps can easily be extended.publishedVersio

The Etiology of Multiple Sclerosis: Genetic Evidence for the Involvement of the Human Endogenous Retrovirus HERV-Fc1

We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis