46 research outputs found

    Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

    Get PDF
    The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

    XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining

    Get PDF
    International audienceThe Ku70-Ku80 (Ku) heterodimer binds rapidly and tightly to the ends of DNA double-strand breaks and recruits factors of the non-homologous end-joining (NHEJ) repair pathway through molecular interactions that remain unclear. We have determined crystal structures of the Ku-binding motifs (KBM) of the NHEJ proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex. The two KBM motifs bind remote sites of the Ku80 alpha/beta domain. The X-KBM occupies an internal pocket formed by an unprecedented large outward rotation of the Ku80 alpha/beta domain. We observe independent recruitment of the APLF-interacting protein XRCC4 and of XLF to laser-irradiated sites via binding of A- and X-KBMs, respectively, to Ku80. Finally, we show that mutation of the X-KBM and A-KBM binding sites in Ku80 compromises both the efficiency and accuracy of end joining and cellular radiosensitivity. A- and X-KBMs may represent two initial anchor points to build the intricate interaction network required for NHEJ

    Modélisation et simulation numérique d'oligomères du MM 2.1.2 (contribution à l'analyse de ses propriétés d'agrégation)

    No full text
    Les nanotechnologies utilisées dans le traitement de certaines pathologies permettent actuellement de concevoir des systèmes transporteurs acheminant les principes actifs jusqu'à leurs cibles. Les enjeux sont considérables puisque ces systèmes offrent une protection au principe actif, augmentent la pénétration intracellulaire et le ciblage et donc réduisent les doses à administrer et les effets secondaires. Ces systèmes, appelés vecteurs, peuvent être constitués de polymère biodégradable. Le poly(méthylidène malonate 2.1.2), développé par la société de recherche pharmaceutique Virsol, est un des polymères utilisables dans ce domaine. Il présente une faible toxicité et la synthèse relativement aisée de particules à base de ce polymère rend son développement intéressant. Une étude complète de ses propriétés d'agrégation a nécessité la modélisation et la simulation numérique en solvatation explicite d'oligomères de méthylidène malonate 2.1.2. Après un chapitre d'introduction sur les vecteurs colloïdaux, nous présenterons les résultats obtenus en dynamique moléculaire puis ceux issus de calculs ab initio.ORLEANS-BU Sciences (452342104) / SudocSudocFranceF

    Crystallisation and molecular mobilities in liquid and glassy states of a MXD6 polyamide

    No full text
    International audienceThe dynamic of molecular mobilities occurring above and below the glass transition of a polyamide called MXD6 have been investigated on samples with different degrees of crystallinity. The fragility index (m) has been evaluated for a fully amorphous material and it was found that m = 180 classifies this material as fragile in regard to the strong-fragile glass forming liquid concept. For semi-crystalline samples, the results show two relaxation processes at the glass transition. One can be attributed to the molecular mobility existing in the free amorphous domain, and the second peak to a molecular mobility existing in a rigid amorphous domain as proposed by the '3-phase model'. The existence of these two phenomena does not allow a correct determination of the fragility index for such semi-crystalline materials by means of calorimetric investigation

    Crystallisation and molecular mobilities in liquid and glassy states of a MXD6 polyamide

    No full text
    International audienceThe dynamic of molecular mobilities occurring above and below the glass transition of a polyamide called MXD6 have been investigated on samples with different degrees of crystallinity. The fragility index (m) has been evaluated for a fully amorphous material and it was found that m = 180 classifies this material as fragile in regard to the strong-fragile glass forming liquid concept. For semi-crystalline samples, the results show two relaxation processes at the glass transition. One can be attributed to the molecular mobility existing in the free amorphous domain, and the second peak to a molecular mobility existing in a rigid amorphous domain as proposed by the '3-phase model'. The existence of these two phenomena does not allow a correct determination of the fragility index for such semi-crystalline materials by means of calorimetric investigation
    corecore