INGENUE : une modélisation intergénérationnelle et universelle.

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Etude du rôle de l'hélicase Srs2 dans la régulation de la recombinaison homologue chez la levure Saccharomyces cerevisiae

La recombinaison homologue (RH) est nécessaire au maintien de l'intégrité du génome. Cependant, elle peut parfois se révéler dangereuse en formant des structures toxiques ou en générant des réarrangements chromosomiques néfastes. Chez S. cerevisiae, l hélicase Srs2 est capable d inhiber la RH via l élimination de la protéine Rad51 de l ADNsb.Deux nouveaux mutants srs2R1 et srs2R3 ont été identifiés au laboratoire. Les résultats génétiques et biochimiques obtenus suggèrent qu ils ne sont plus capables d inhiber la recombinaison homologue à la fourche de réplication. Les données montrent de plus que le recrutement de Srs2 par PCNA sumoylé n est pas essentiel à l élimination des intermédiaires toxiques de recombinaison. Srs2 est également nécessaire pour la régulation des étapes tardives de la RH. En effet, Srs2 inhibe fortement la formation de crossing over probablement en favorisant une voie de résolution appelée SDSA. Nous montrons dans cette étude que Srs2 purifié possède in vitro l ensemble des activités biochimiques requises pour permettre l utilisation du SDSA.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

L'effet réseau alimente des actions collectives de prévention en santé très significatives

International audienceLa prévention et promotion en santé occupe une place non négligeable dans les contrats locaux de santé, d'après le projet de recherche CLOTERRES porté par un consortium pluridisciplinaire, dont l'EHESP. Les collectivités sont alors invitées à s'engager dans cette voie même si la santé n'est pas dans leur champ de compétences. C'est le bon moment

L'effet réseau alimente des actions collectives de prévention en santé très significatives

International audienc

Replication-Fork Stalling and Processing at a Single Psoralen Interstrand Crosslink in Xenopus Egg Extracts

Interstrand crosslink (ICL)-inducing agents block the separation of the two DNA strands. They prevent transcription and replication and are used in clinics for the treatment of cancer and skin diseases. Here, we have introduced a single psoralen ICL at a specific site in plasmid DNA using a triplex-forming-oligonucleotide (TFO)-psoralen conjugate and studied its repair in Xenopus egg extracts that support nuclear assembly and replication of plasmid DNA. Replication forks arriving from either side stalled at the psoralen ICL. In contrast to previous observations with other ICL-inducing agents, the leading strands advanced up to the lesion without any prior pausing. Subsequently, incisions were introduced on one parental strand on both sides of the ICL. These incisions could be detected whether one or both forks reached the ICL. Using small molecule inhibitors, we found that the ATR-Chk1 pathway, but not the ATM-Chk2 pathway, stimulated both the incision step and the subsequent processing of the broken replication intermediates. Our results highlight both similarities and differences in fork stalling and repair induced by psoralen and by other ICL-forming agents

The Srs2 helicase activity is stimulated by Rad51 Filaments on dsDNA : Implications for crossover incidence during mitotic recombination.

International audienc

Are French local health contracts promising in addressing determinants of diet and physical activity?

Background: There is a consensus on the need to transform the built, economic and socio-cultural environments to promote healthy eating (HE) and physical activity (PA). Yet, limited capacity and the biomedicalisation of public health are often blamed for steering investments towards individual risk factors. In France, local health contracts (LHCs) agreed between a regional health agency (RHA) and a local government could improve health promotion strategies. We examined how LHCs take into account the environmental determinants of HE and PA. Methods: Using the CLoterreS national census, we analysed a stratified random sample of 53 LHCs with a view to identify if actions target individual (knowledge, skills, etc.) or environmental (interpersonal, organisational, community or political) determinants. To this end, we developed an instrument drawing from different typologies of action and consensus documents to assess the integration of the socioecological approach in programmes. We ran a series of interviews with RHA staff (n = 39) and local actors (n = 23) to put into context our results.Results: Out of 53 LHCs, 42 included at least one action on HE or PA. For these topics, there was a higher proportion of actions targeting individuals (83% and 76% per contract, respectively) than environments (51% and 58%). For the latter, actions on interpersonal determinants (e.g. family) were the most common. However, we also found instances of actions on more distal ones (e.g. to improve nutrition standards in school canteens and walkability). Contextual factors such as local priorities, past experience with health promotion and the involvement of local actors in needs assessment and action planning may influence such orientations.Conclusions: LHCs constitute a promising avenue to address the environmental determinants of health-related behaviours. A key feature of this instrument is its capacity to develop intersectoral strategies. Further research will show if LHCs deliver on their action plan

Are French local health contracts promising in addressing determinants of diet and physical activity?

Background: There is a consensus on the need to transform the built, economic and socio-cultural environments to promote healthy eating (HE) and physical activity (PA). Yet, limited capacity and the biomedicalisation of public health are often blamed for steering investments towards individual risk factors. In France, local health contracts (LHCs) agreed between a regional health agency (RHA) and a local government could improve health promotion strategies. We examined how LHCs take into account the environmental determinants of HE and PA. Methods: Using the CLoterreS national census, we analysed a stratified random sample of 53 LHCs with a view to identify if actions target individual (knowledge, skills, etc.) or environmental (interpersonal, organisational, community or political) determinants. To this end, we developed an instrument drawing from different typologies of action and consensus documents to assess the integration of the socioecological approach in programmes. We ran a series of interviews with RHA staff (n = 39) and local actors (n = 23) to put into context our results.Results: Out of 53 LHCs, 42 included at least one action on HE or PA. For these topics, there was a higher proportion of actions targeting individuals (83% and 76% per contract, respectively) than environments (51% and 58%). For the latter, actions on interpersonal determinants (e.g. family) were the most common. However, we also found instances of actions on more distal ones (e.g. to improve nutrition standards in school canteens and walkability). Contextual factors such as local priorities, past experience with health promotion and the involvement of local actors in needs assessment and action planning may influence such orientations.Conclusions: LHCs constitute a promising avenue to address the environmental determinants of health-related behaviours. A key feature of this instrument is its capacity to develop intersectoral strategies. Further research will show if LHCs deliver on their action plan