Dysfunction and toxicity of damaged proteins in the etiology of aging and age-related degenerative and malignant diseases

Health can be defined as a harmony, or homeostasis, of the activities of thousands of different proteins, whereas aging and diseases result from their disharmony manifested at the levels of cells and tissues. Such disharmony is caused primarily by dysfunction and toxicity of misfolded proteins damaged by oxidation. This is an overview of key data that inspired new concepts allowing interpretation and inte- gration of the scientific literature on aging and age-related diseases. These concepts suggest strategies for prevention and attenuation of age-related degenerative and malig- nant diseases mimicking the life of super-centenarians

The λ Red Proteins Promote Efficient Recombination between Diverged Sequences: Implications for Bacteriophage Genome Mosaicism

Genome mosaicism in temperate bacterial viruses (bacteriophages) is so great that it obscures their phylogeny at the genome level. However, the precise molecular processes underlying this mosaicism are unknown. Illegitimate recombination has been proposed, but homeologous recombination could also be at play. To test this, we have measured the efficiency of homeologous recombination between diverged oxa gene pairs inserted into λ. High yields of recombinants between 22% diverged genes have been obtained when the virus Red Gam pathway was active, and 100 fold less when the host Escherichia coli RecABCD pathway was active. The recombination editing proteins, MutS and UvrD, showed only marginal effects on λ recombination. Thus, escape from host editing contributes to the high proficiency of virus recombination. Moreover, our bioinformatics study suggests that homeologous recombination between similar lambdoid viruses has created part of their mosaicism. We therefore propose that the remarkable propensity of the λ-encoded Red and Gam proteins to recombine diverged DNA is effectively contributing to mosaicism, and more generally, that a correlation may exist between virus genome mosaicism and the presence of Red/Gam-like systems

Mécanismes de la réparation du DNA et leurs rôles biologiques

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

The mechanism of DNA repair in heavily irradiated Deinococcus radiodurans

Deinococcus radiodurans est une bactérie qui présente une exceptionnelle résistance à de nombreux stress génotoxiques qui fragmentent notamment son génome en une multitude de segments. Nous avons montré que la réassociation des fragments générés dépend d un nouveau mécanisme moléculaire, qui implique l activité interdépendante de la recombinaison et de la réplication de l ADN. Dans une première étape, la majorité des fragments est réassemblée par la voie de synthèse étendue par appariement des brins (extended synthesis-dependant strand annealing ou ESDSA). Les protéines RecA et RadA initient la synthèse de nouveaux brins en utilisant comme matrice l ADN complémentaire d un fragment chevauchant appartenant à une autre copie génomique de la même cellule. Polymérase III est essentielle pour l initiation de la synthèse réparatrice de l ADN, tandis que les ADN Polymérases III et I sont nécessaires pour l élongation de la synthèse. Dans une seconde étape, les longs fragments linéaires reconstitués sont réassemblés en chromosomes circulaires par recombinaison homologue dépendante de RecA.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF