Δευτέρα, 18 Σεπτεμβρίου 2017

Localization of Cdc7 Protein Kinase During DNA Replication in Saccharomyces cerevisiae

DDK, a conserved serine-threonine protein kinase composed of a regulatory subunit, Dbf4, and a catalytic subunit, Cdc7, is essential for DNA replication initiation during S phase of the cell cycle through MCM2-7 helicase phosphorylation. The biological significance of DDK is well characterized, but the full mechanism of how DDK associates with substrates remains unclear. Cdc7 is bound to chromatin in the Saccharomyces cerevisiae genome throughout the cell cycle, but there is little empirical evidence as to specific Cdc7 binding locations. Using biochemical and genetic techniques, this study investigated the specific localization of Cdc7 on chromatin. The Calling Cards method, using Ty5 retrotransposons as a marker for DNA-protein binding, suggests Cdc7 kinase is preferentially bound to genomic DNA known to replicate early in S phase, including centromeres and origins of replication. We also discovered Cdc7 binding throughout the genome, which may be necessary to initiate other cellular processes, including meiotic recombination and translesion synthesis. A kinase-dead Cdc7 point mutation increases the Ty5 retrotransposon integration efficiency and a 55 amino acid C-terminal truncation of Cdc7, unable to bind Dbf4, reduces Cdc7 binding suggesting a requirement for Dbf4 to stabilize Cdc7 on chromatin during S phase. Chromatin immunoprecipitation demonstrates that Cdc7 binding near specific origins changes during S phase. Our results suggest a model where Cdc7 is loosely bound to chromatin during G1. At the G1/S transition, Cdc7 binding to chromatin is increased and stabilized, preferentially at sites that may become origins, in order to carry out a variety of cellular processes.



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U isotopes distribution in the Lower Rhone River and its implication on radionuclides disequilibrium within the decay series

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Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Mathilde Zebracki, Xavier Cagnat, Stéphanie Gairoard, Nicolas Cariou, Frédérique Eyrolle-Boyer, Béatrice Boulet, Christelle Antonelli
The large rivers are main pathways for the delivery of suspended sediments into coastal environments, affecting the biogeochemical fluxes and the ecosystem functioning. The radionuclides from 238U and 232Th—series can be used to understand the dynamic processes affecting both catchment soil erosion and sediment delivery to oceans. Based on annual water discharge the Rhone River represents the largest river of the Mediterranean Sea. The Rhone valley also represents the largest concentration in nuclear power plants in Europe. A radioactive disequilibrium between particulate 226Ra(p) and 238U(p) was observed in the suspended sediment discharged by the Lower Rhone River (Eyrolle et al. 2012), and a fraction of particulate 234Th was shown to derive from dissolved 238U(d) (Zebracki et al. 2013). This extensive study has investigated the dissolved U isotopes distribution in the Lower Rhone River and its implication on particulate radionuclides disequilibrium within the decay series. The suspended sediment and filtered river waters were collected at low and high water discharges. During the 4—months of the study, two flood events generated by the Rhone southern tributaries were monitored. In river waters, the total U(d) concentration and U isotopes distribution were obtained through Q-ICP-MS measurements. The Lower Rhone River has displayed non-conservative U—behavior, and the variations in U(d) concentration between southern tributaries were related to the differences in bedrock lithology. The artificially occurring 236U was detected in the Rhone River at low water discharges, and was attributed to the liquid releases from nuclear industries located along the river. The (235U/238U)(d) activity ratio (=AR) in river waters was representative of the 235U natural abundance on Earth. The (226Ra/238U)(p) AR in suspended sediment has indicated a radioactive disequilibrium (average 1.3 ± 0.1). The excess of 234Th in suspended sediment =(234Thxs(p)) was apparent solely at low water discharges. The activity of 234Thxs(p) was calculated through gamma measurements and ranged from unquantifiable to 56 ± 14 Bq kg−1. The possibility of using 234Th as a tracer for the suspended sediment dynamics in large Mediterranean river was then discussed.



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P 119 Implicit and explicit motor learning in Parkinson’s disease and spinocerebellar ataxia

Motor learning is a fundamental skill in everyday life. Acquisition of new motor skills engage cortico-striatal-cerebellar connectivity. Particularly patients with Parkinson"s disease and spinocerebellar ataxia are affected but these patient groups fundamentally differ in their behaviour in implicit motor learning tasks. Yet little is known about motor learning in relation to rule-based motor sequence learning. The aim of the current study was to test whether there are differences or similarities in implicit and explicit motor learning tasks in PD, SCA and healthy controls.

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Mother, Jugs, Speed stretcher scene

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Genome-wide compound heterozygote analysis highlights alleles associated with adult height in Europeans

Abstract

Adult height is the most widely genetically studied common trait in humans; however, the trait variance explainable by currently known height-associated single nucleotide polymorphisms (SNPs) identified from the previous genome-wide association studies (GWAS) is yet far from complete given the high heritability of this complex trait. To exam if compound heterozygotes (CH) may explain extra height variance, we conducted a genome-wide analysis to screen for CH in association with adult height in 10,631 Dutch Europeans enriched with extremely tall people, using our recently developed method implemented in the software package CollapsABEL. The analysis identified six regions (3q23, 5q35.1, 6p21.31, 6p21.33, 7q21.2, and 9p24.3), where multiple pairs of SNPs as CH showed genome-wide significant association with height (P < 1.67 × 10−10). Of those, 9p24.3 represents a novel region influencing adult height, whereas the others have been highlighted in the previous GWAS on height based on analysis of individual SNPs. A replication analysis in 4080 Australians of European ancestry confirmed the significant CH-like association at 9p24.3 (P < 0.05). Together, the collapsed genotypes at these six loci explained 2.51% of the height variance (after adjusting for sex and age), compared with 3.23% explained by the 14 top-associated SNPs at 14 loci identified by traditional GWAS in the same data set (P < 5 × 10−8). Overall, our study empirically demonstrates that CH plays an important role in adult height and may explain a proportion of its "missing heritability". Moreover, our findings raise promising expectations for other highly polygenic complex traits to explain missing heritability identifiable through CH-like associations.



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Development: Transcriptomic blueprints

Nature Reviews Genetics. doi:10.1038/nrg.2017.77

Author: Linda Koch



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Editorial board members

Publication date: July 2017
Source:Mutation Research/Reviews in Mutation Research, Volume 773





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In this issue



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Publication schedule for 2017



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Cover Image, Volume 173A, Number 10, October 2017

Thumbnail image of graphical abstract

The cover image, by Rani A. Bashir et al., is based on the Original Article Lin-Gettig syndrome: Craniosynostosis expands the spectrum of the KAT6B related disorders, DOI: 10.1002/ajmg.a.38355.



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Table of Contents, Volume 173A, Number 10, October 2017



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New intellectual disability syndrome identified



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Genome-wide cell free fetal DNA screening spots variations standard screening doesn't



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