Limited TTP supply affects telomere length regulation in a telomerase-independent fashion

An adequate supply of nucleotides is essential for DNA replication and DNA repair. Moreover, inhibition of TTP synthesis can cause cell death by a poorly characterized mechanism called thymine-less death. In the yeast Saccharomyces cerevisiae, the genes encoding thymidylate synthetase (CDC21) and thymidylate kinase (CDC8) are both essential for de novo TTP synthesis. The effects of temperature-sensitive mutations in these genes have been characterized and, curiously, the phenotypes displayed by cells harboring them include shortened telomeric repeat tracts. This finding raised the possibility that the enzyme telomerase is very sensitive to TTP-pools. We tested this possibility in vivo by assessing telomerase-dependent extension in situations of lowered TTP supply. The results show that the above-mentioned short telomere phenotype is not a consequence of an inability of telomerase to elongate telomeres when TTP synthesis is impaired. Moreover, this telomere shortening was abolished in cells harboring a mutation in DNA polymerase α. Previously, this same mutation was shown to affect the coordination between conventional replication and telomerase-mediated extension. These results thus re-emphasize the importance of the interplay between conventional replication and telomerase-mediated addition of telomeric repeats in telomere replication

Effet des perturbations de la synthèse des nucléotides sur la réplication des télomères

Les nucléotides sont nécessaires pour la réplication et la réparation du génome. Un déséquilibre dans le ratio entre les différents nucléotides a des effets variés sur les cellules, pouvant entre autres provoquer des mutations et la carcinogénèse chez les mammifères. Chez Saccharomyces cerevisiae , une mutation dans les gènes codant pour la thymidilate synthase ( CDC21 ) ou la thymidilate kinase ( CDC8 ), impliqués dans la synthèse des dTTP, provoque un raccourcissement des télomères. De plus, l'inhibition complète de la synthèse des dTTP provoque la mort des cellules par" thymineless death" (TLD). Avec cette étude, nous démontrons que la diminution de la synthèse des dTTP, ainsi que la diminution de la synthèse de tous les nucléotides provoquent un raccourcissement des télomères. Ce défaut télomérique serait provoqué par une incapacité de la réplication semi-conservative à répliquer entièrement les télomères, et d'une incapacité de bien coordonner la fourche de réplication avec la télomérase. En plus d'ajouter aux connaissances sur les répercussions d'un déséquilibre de la synthèse des nucléotides, ces résultats démontreraient une fois de plus, l'importance d'une bonne coordination entre la fourche de réplication et la télomérase pour une réplication et un maintien adéquat des télomères

Analyse de l'influence de la chromatine et de l'hétérochromatine dans la réparation des dommages créés par les rayons UV dans l'ADN chez la levure Saccharomyces cerevisiae

Les rayons UV du soleil causent une variété de dommages dans l'ADN, parmi lesquels les dimères cyclobutilyques de pyrimidines (CPD) sont considérés comme hautement toxiques et dommageables pour un organisme. Par conséquent, il est important de comprendre comment la machinerie de réparation par excision des nucléotides (la NER), assure la réparation in vivo des CPD présents dans l'ADN empaqueté sous forme de chromatine. Il est connu que la présence du nucléosome inhiberait la NER, mais les détails fonctionnels demeurent mal compris, de même que les mécanismes cellulaires nécessaires pour contourner cette inhibition offerte par la chromatine. Chez la levure Saccharomyces cerevisiae, les gènes SIR (SIR1, SIR2, SIR3 et SIR4 ) permettent la formation d'une structure hétérochromatique sur le locus du type sexuel et les télomères. Cependant, l'impact de cette hétérochromatine sur la réparation des CPD est très peu étudié.Les travaux présentés dans cette thèse de doctorat ont permis de caractériser l'impact des gènes SIR dans la survie des cellules après irradiation aux rayons UV, de même que dans la réparation de l'ADN des régions hétérochromatiques. Premièrement, à l'aide d'une méthode basée sur le suivi de la croissance en milieu de culture liquide, nous avons démontré que les mutants sir[delta] sont plus résistants aux rayons UV par rapport aux cellules de types sauvages. Ce phénotype serait relié à l'effet de pseudo-diploïdie présent dans ces mutants, et plus précisément à la recombinaison homologue en phase G2/M du cycle cellulaire.Les protéines Sir ne joueraient donc pas un rôle directement dans la réparation des CPD. Par la suite, nous avons procédé à l'analyse de la cinétique de réparation de l'ADN du locus du type sexuel et des télomères dans des cellules de type sauvage et des mutants si2r[delta], sir3[delta], et rad26[delta] . À partir des résultats obtenus, nous avons pu tirer différentes conclusions préliminaires laissant croire que la présence de l'hétérochromatine faite par les protéines Sir n'inhiberait pas davantage la réparation par rapport à la présence des nucléosomes, du moins dans les régions sous-télomériques. De plus, nos résultats démontreraient que la réparation couplée à la transcription pourrait jouer un rôle important dans la réparation de ces régions. Ces hypothèses devront évidemment être testées

Reaction-Diffusion Processes as Physical Realizations of Hecke Algebras

We show that the master equation governing the dynamics of simple diffusion and certain chemical reaction processes in one dimension give time evolution operators (Hamiltonians) which are realizations of Hecke algebras. In the case of simple diffusion one obtains, after similarity transformations, reducible hermitian representations while in the other cases they are non-hermitian and correspond to supersymmetric quotients of Hecke algebras.Comment: Latex, 6 pages, BONN-HE-93.1

On Reconfiguring Tree Linkages: Trees can Lock

It has recently been shown that any simple (i.e. nonintersecting) polygonal chain in the plane can be reconfigured to lie on a straight line, and any simple polygon can be reconfigured to be convex. This result cannot be extended to tree linkages: we show that there are trees with two simple configurations that are not connected by a motion that preserves simplicity throughout the motion. Indeed, we prove that an $N$-link tree can have $2^{\Omega(N)}$ equivalence classes of configurations.Comment: 16 pages, 6 figures Introduction reworked and references added, as the main open problem was recently close

The Distance Geometry of Music

We demonstrate relationships between the classic Euclidean algorithm and many other fields of study, particularly in the context of music and distance geometry. Specifically, we show how the structure of the Euclidean algorithm defines a family of rhythms which encompass over forty timelines (\emph{ostinatos}) from traditional world music. We prove that these \emph{Euclidean rhythms} have the mathematical property that their onset patterns are distributed as evenly as possible: they maximize the sum of the Euclidean distances between all pairs of onsets, viewing onsets as points on a circle. Indeed, Euclidean rhythms are the unique rhythms that maximize this notion of \emph{evenness}. We also show that essentially all Euclidean rhythms are \emph{deep}: each distinct distance between onsets occurs with a unique multiplicity, and these multiplicies form an interval $1,2,...,k-1$. Finally, we characterize all deep rhythms, showing that they form a subclass of generated rhythms, which in turn proves a useful property called shelling. All of our results for musical rhythms apply equally well to musical scales. In addition, many of the problems we explore are interesting in their own right as distance geometry problems on the circle; some of the same problems were explored by Erd\H{o}s in the plane.Comment: This is the full version of the paper: "The distance geometry of deep rhythms and scales." 17th Canadian Conference on Computational Geometry (CCCG '05), University of Windsor, Canada, 200

Repair of UV-induced DNA lesions in natural Saccharomyces cerevisiae telomeres is moderated by Sir2 and Sir3, and inhibited by yKu–Sir4 interaction

Ultraviolet light (UV) causes DNA damage that is removed by nucleotide excision repair (NER). UVinduced DNA lesions must be recognized and repaired in nucleosomal DNA, higher order structures of chromatin and within different nuclear subcompartments. Telomeric DNA is made of short tandem repeats located at the ends of chromosomes and their maintenance is critical to prevent genome instability. In Saccharomyces cerevisiae the chromatin structure of natural telomeres is distinctive and contingent to telomeric DNA sequences. Namely, nucleosomes and Sir proteins form the heterochromatin like structure of X-type telomeres, whereas a more open conformation is present at Y’-type telomeres. It is proposed that there are no nucleosomes on the most distal telomeric repeat DNA, which is bound by a complex of proteins and folded into higher order structure. How these structures affect NER is poorly understood. Our data indicate that the X-type, but not the Y’-type, sub-telomeric chromatin modulates NER, a consequence of Sir protein-dependent nucleosome stability. The telomere terminal complex also prevents NER, however, this effect is largely dependent on the yKu–Sir4 interaction, but Sir2 and Sir3 independent

Perception of Rhythmic Similarity in Flamenco Music: Comparing Musicians and Non-Musicians.

Background in Music Psychology. Previous research on rhythmic perception has highlighted differences between novice listeners and musicians in their ability to label perceived differences as well as strategies for representing musical structures. Novice listeners tend to focus on “surface” features while musicians tend to focus on the underlying rhythmic structure and develop a specific vocabulary. Furthermore, there is evidence that changes in tempo affect novices’ perception of rhythm

Pleistocene climate change promoted rapid diversification of aquatic invertebrates in Southeast Australia

Background: The Pleistocene Ice Ages were the most recent geohistorical event of major global impact, but their consequences for most parts of the Southern hemisphere remain poorly known. We investigate a radiation of ten species of Sternopriscus, the most species-rich genus of epigean Australian diving beetles. These species are distinct based on genital morphology but cannot be distinguished readily by mtDNA and nDNA because of genotype sharing caused by incomplete lineage sorting. Their genetic similarity suggests a Pleistocene origin. Results: We use a dataset of 3858 bp of mitochondrial and nuclear DNA to reconstruct a phylogeny of Sternopriscus using gene and species trees. Diversification analyses support the finding of a recent rapid speciation event with estimated speciation rates of up to 2.40 species per MY, which is considerably higher than the proposed average rate of 0.16 species per MY for insects. Additionally, we use ecological niche modeling and analyze data on habitat preferences to test for niche divergence between species of the recent Sternopriscus radiation. These analyses show that the species can be characterized by a set of ecological variables referring to habitat, climate and altitude. Conclusions: Our results suggest that the repeated isolation of populations in glacial refugia might have led to divergent ecological adaptations and the fixation of morphological traits supporting reproductive isolation and therefore may have promoted speciation. The recent Sternopriscus radiation fulfills many characteristics of a species flock and would be the first described example of an aquatic insect species flock. We argue that the species of this group may represent a stage in speciation past the species flock condition because of their mostly broad and often non-overlapping ranges and preferences for different habitat types.Organismic and Evolutionary Biolog