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S Domenichini M Benhamed G De Jaeger E Van De Slijke S Blanchet M Bourge L De Veylder C Bergounioux C Raynaud 《The Plant cell》2012,24(7):2779-2791
Meristems retain the ability to divide throughout the life cycle of plants, which can last for over 1000 years in some species. Furthermore, the germline is not laid down early during embryogenesis but originates from the meristematic cells relatively late during development. Thus, accurate cell cycle regulation is of utmost importance to avoid the accumulation of mutations during vegetative growth and reproduction. The Arabidopsis thaliana genome encodes two homologs of the replication licensing factor CDC10 Target1 (CDT1), and overexpression of CDT1a stimulates DNA replication. Here, we have investigated the respective functions of Arabidopsis CDT1a and CDT1b. We show that CDT1 proteins have partially redundant functions during gametophyte development and are required for the maintenance of genome integrity. Furthermore, CDT1-RNAi plants show endogenous DNA stress, are more tolerant than the wild type to DNA-damaging agents, and show constitutive induction of genes involved in DNA repair. This DNA stress response may be a direct consequence of reduced CDT1 accumulation on DNA repair or may relate to the ability of CDT1 proteins to form complexes with DNA polymerase ε, which functions in DNA replication and in DNA stress checkpoint activation. Taken together, our results provide evidence for a crucial role of Arabidopsis CDT1 proteins in genome stability. 相似文献
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Summary We present an adaptive percentile modified Wilcoxon rank sum test for the two‐sample problem. The test is basically a Wilcoxon rank sum test applied on a fraction of the sample observations, and the fraction is adaptively determined by the sample observations. Most of the theory is developed under a location‐shift model, but we demonstrate that the test is also meaningful for testing against more general alternatives. The test may be particularly useful for the analysis of massive datasets in which quasi‐automatic hypothesis testing is required. We investigate the power characteristics of the new test in a simulation study, and we apply the test to a microarray experiment on colorectal cancer. These empirical studies demonstrate that the new test has good overall power and that it succeeds better in finding differentially expressed genes as compared to other popular tests. We conclude that the new nonparametric test is widely applicable and that its power is comparable to the power of the Baumgartner‐Weiß‐Schindler test. 相似文献
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Transcriptional control of the cell cycle 总被引:1,自引:0,他引:1
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Efficient mouse transgenesis using Gateway-compatible ROSA26 locus targeting vectors and F1 hybrid ES cells 下载免费PDF全文
Omar Nyabi Michael Naessens Katharina Haigh Agnieszka Gembarska Steven Goossens Marion Maetens Sarah De Clercq Benjamin Drogat Lieven Haenebalcke Sonia Bartunkova Ilse De Vos Bram De Craene Mansour Karimi Geert Berx Andras Nagy Pierre Hilson Jean-Christophe Marine Jody J. Haigh 《Nucleic acids research》2009,37(7):e55
The ability to rapidly and efficiently generate reliable Cre/loxP conditional transgenic mice would greatly complement global high-throughput gene targeting initiatives aimed at identifying gene function in the mouse. We report here the generation of Cre/loxP conditional ROSA26-targeted ES cells within 3–4 weeks by using Gateway® cloning to build the target vectors. The cDNA of the gene of interest can be expressed either directly by the ROSA26 promoter providing a moderate level of expression or by a CAGG promoter placed in the ROSA26 locus providing higher transgene expression. Utilization of F1 hybrid ES cells with exceptional developmental potential allows the production of germ line transmitting, fully or highly ES cell-derived mice by aggregation of cells with diploid embryos. The presented streamlined procedures accelerate the examination of phenotypical consequences of transgene expression. It also provides a unique tool for comparing the biological activity of polymorphic or splice variants of a gene, or products of different genes functioning in the same or parallel pathways in an overlapping manner. 相似文献
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Bongartz JP Stokbroekx R Van der Aa M Luyckx M Willems M Ceusters M Meerpoel L Smets G Jansen T Wouters W Bowden C Valletta L Herb M Tominovich R Tuman R 《Bioorganic & medicinal chemistry letters》2002,12(4):589-591
General screening for inhibitors of microvessel growth in vitro in the rat aortic ring assay led to the discovery of a novel series of thiadiazole pyridazine compounds with potential anti-angiogenic activity. Chemical optimization produced orally active compounds with potent in vitro and in vivo anti-angiogenesis and anti-tumor activities. 相似文献
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Thomas Eekhout Martina Dvorackova Jos Antonio Pedroza Garcia Martina Nespor Dadejova Pooneh Kalhorzadeh Hilde Van den Daele Ilse Vercauteren Jiri Fajkus Lieven De Veylder 《Plant physiology》2021,186(4):1893
The WEE1 and ATM AND RAD3-RELATED (ATR) kinases are important regulators of the plant intra-S-phase checkpoint; consequently, WEE1KO and ATRKO roots are hypersensitive to replication-inhibitory drugs. Here, we report on a loss-of-function mutant allele of the FASCIATA1 (FAS1) subunit of the chromatin assembly factor 1 (CAF-1) complex that suppresses the phenotype of WEE1- or ATR-deficient Arabidopsis (Arabidopsis thaliana) plants. We demonstrate that lack of FAS1 activity results in the activation of an ATAXIA TELANGIECTASIA MUTATED (ATM)- and SUPPRESSOR OF GAMMA-RESPONSE 1 (SOG1)-mediated G2/M-arrest that renders the ATR and WEE1 checkpoint regulators redundant. This ATM activation accounts for the telomere erosion and loss of ribosomal DNA that are described for fas1 plants. Knocking out SOG1 in the fas1 wee1 background restores replication stress sensitivity, demonstrating that SOG1 is an important secondary checkpoint regulator in plants that fail to activate the intra-S-phase checkpoint. 相似文献
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