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991.
José Antonio Pedroza-Garcia Séverine Domenichini Christelle Mazubert Mickael Bourge Charles White Elodie Hudik Rémi Bounon Zakia Tariq Etienne Delannoy Ivan del?Olmo Manuel Pi?eiro Jose Antonio Jarillo Catherine Bergounioux Moussa Benhamed Cécile Raynaud 《Nucleic acids research》2016,44(15):7251-7266
Faithful DNA replication maintains genome stability in dividing cells and from one generation to the next. This is particularly important in plants because the whole plant body and reproductive cells originate from meristematic cells that retain their proliferative capacity throughout the life cycle of the organism. DNA replication involves large sets of proteins whose activity is strictly regulated, and is tightly linked to the DNA damage response to detect and respond to replication errors or defects. Central to this interconnection is the replicative polymerase DNA Polymerase ϵ (Pol ϵ) which participates in DNA replication per se, as well as replication stress response in animals and in yeast. Surprisingly, its function has to date been little explored in plants, and notably its relationship with DNA Damage Response (DDR) has not been investigated. Here, we have studied the role of the largest regulatory sub-unit of Arabidopsis DNA Pol ϵ: DPB2, using an over-expression strategy. We demonstrate that excess accumulation of the protein impairs DNA replication and causes endogenous DNA stress. Furthermore, we show that Pol ϵ dysfunction has contrasting outcomes in vegetative and reproductive cells and leads to the activation of distinct DDR pathways in the two cell types. 相似文献
992.
993.
CK2‐regulated schwannomin‐interacting protein IQCJ‐SCHIP‐1 association with AnkG contributes to the maintenance of the axon initial segment 下载免费PDF全文
Marie‐Jeanne Papandréou Hélène Vacher Marie‐Pierre Fache Esther Klingler Fanny Rueda‐Boroni Géraldine Ferracci Claire Debarnot Christelle Pipéroglou Gontzal Garcia Del Caño Laurence Goutebroze Bénédicte Dargent 《Journal of neurochemistry》2015,134(3):527-537
The axon initial segment (AIS) plays a central role in electrogenesis and in the maintenance of neuronal polarity. Its molecular organization is dependent on the scaffolding protein ankyrin (Ank) G and is regulated by kinases. For example, the phosphorylation of voltage‐gated sodium channels by the protein kinase CK2 regulates their interaction with AnkG and, consequently, their accumulation at the AIS. We previously showed that IQ motif containing J‐Schwannomin‐Interacting Protein 1 (IQCJ‐SCHIP‐1), an isoform of the SCHIP‐1, accumulated at the AIS in vivo. Here, we analyzed the molecular mechanisms involved in IQCJ‐SCHIP‐1‐specific axonal location. We showed that IQCJ‐SCHIP‐1 accumulation in the AIS of cultured hippocampal neurons depended on AnkG expression. Pull‐down assays and surface plasmon resonance analysis demonstrated that AnkG binds to CK2‐phosphorylated IQCJ‐SCHIP‐1 but not to the non‐phosphorylated protein. Surface plasmon resonance approaches using IQCJ‐SCHIP‐1, SCHIP‐1a, another SCHIP‐1 isoform, and their C‐terminus tail mutants revealed that a segment including multiple CK2‐phosphorylatable sites was directly involved in the interaction with AnkG. Pharmacological inhibition of CK2 diminished both IQCJ‐SCHIP‐1 and AnkG accumulation in the AIS. Silencing SCHIP‐1 expression reduced AnkG cluster at the AIS. Finally, over‐expression of IQCJ‐SCHIP‐1 decreased AnkG concentration at the AIS, whereas a mutant deleted of the CK2‐regulated AnkG interaction site did not. Our study reveals that CK2‐regulated IQJC‐SCHIP‐1 association with AnkG contributes to AIS maintenance.
994.
Induced Jasmonate Signaling Leads to Contrasting Effects on Root Damage and Herbivore Performance 总被引:3,自引:0,他引:3
995.
Eugenia Migliavacca Christelle Golzio Katrin M?nnik Ian Blumenthal Edwin?C. Oh Louise Harewood Jack A. Kosmicki Maria?Nicla Loviglio Giuliana Giannuzzi Loyse Hippolyte Anne?M. Maillard Ali?Abdullah Alfaiz p. European Consortium Mieke M. van Haelst Joris Andrieux James F. Gusella Mark J. Daly Jacques S. Beckmann Sébastien Jacquemont Michael E. Talkowski Nicholas Katsanis Alexandre Reymond 《American journal of human genetics》2015,96(5):784-796
996.
Akil Hamza Erik Tammpere Megan Kofoed Christelle Keong Jennifer Chiang Guri Giaever Corey Nislow Philip Hieter 《Genetics》2015,201(3):1263-1274
While the pace of discovery of human genetic variants in tumors, patients, and diverse populations has rapidly accelerated, deciphering their functional consequence has become rate-limiting. Using cross-species complementation, model organisms like the budding yeast, Saccharomyces cerevisiae, can be utilized to fill this gap and serve as a platform for testing human genetic variants. To this end, we performed two parallel screens, a one-to-one complementation screen for essential yeast genes implicated in chromosome instability and a pool-to-pool screen that queried all possible essential yeast genes for rescue of lethality by all possible human homologs. Our work identified 65 human cDNAs that can replace the null allele of essential yeast genes, including the nonorthologous pair yRFT1/hSEC61A1. We chose four human cDNAs (hLIG1, hSSRP1, hPPP1CA, and hPPP1CC) for which their yeast gene counterparts function in chromosome stability and assayed in yeast 35 tumor-specific missense mutations for growth defects and sensitivity to DNA-damaging agents. This resulted in a set of human–yeast gene complementation pairs that allow human genetic variants to be readily characterized in yeast, and a prioritized list of somatic mutations that could contribute to chromosome instability in human tumors. These data establish the utility of this cross-species experimental approach. 相似文献
997.
Priscilla Henno Christelle Maurey Fran?oise Le Pimpec-Barthes Philippe Devillier Christophe Delclaux Dominique Isra?l-Biet 《Respiratory research》2015,16(1)
Background
Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The bioavailability of the potent vasodilator nitric oxide (NO) depends on competition between NO synthase-3 (NOS3) and arginases for their common substrate (L-arginine). We tested the hypothesis whereby tobacco smoking impairs pulmonary endothelial function via upregulation of the arginase pathway.Methods
Endothelium-dependent vasodilation in response to acetylcholine (Ach) was compared ex vivo for pulmonary vascular rings from 29 smokers and 10 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of L-arginine supplementation, arginase inhibition (by N(omega)-hydroxy-nor-l-arginine, NorNOHA) and NOS3 induction (by genistein) on vasodilation. Protein levels of NOS3 and arginases I and II in the pulmonary arteries were quantified by Western blotting.Results
Overall, vasodilation was impaired in smokers (relative to controls; p < 0.01). Eleven of the 29 smokers (the ED+ subgroup) displayed endothelial dysfunction (defined as the absence of a relaxant response to Ach), whereas 18 (the ED− subgroup) had normal vasodilation. The mean responses to 10−4 M Ach were −23 ± 10% and 31 ± 4% in the ED+ and ED− subgroups, respectively (p < 0.01). Supplementation with L- arginine improved endothelial function in the ED+ subgroup (−4 ± 10% vs. -32 ± 10% in the presence and absence of L- arginine, respectively; p = 0.006), as did arginase inhibition (18 ± 9% vs. -1 ± 9%, respectively; p = 0.0002). Arginase I protein was overexpressed in ED+ samples, whereas ED+ and ED− samples did not differ significantly in terms of NOS3 expression. Treatment with genistein did not significantly improve endothelial function in ED+ samples.Conclusion
Overexpression and elevated activity of arginase I are involved in tobacco-induced pulmonary endothelial dysfunction. 相似文献998.
Christelle Benaud Gaëlle Le Dez Svetlana Mironov Federico Galli David Reboutier Claude Prigent 《EMBO reports》2015,16(4):481-489
Cytokinesis requires the formation of an actomyosin contractile ring between the two sets of sister chromatids. Annexin A2 is a calcium- and phospholipid-binding protein implicated in cortical actin remodeling. We report that annexin A2 accumulates at the equatorial cortex at the onset of cytokinesis and depletion of annexin A2 results in cytokinetic failure, due to a defective cleavage furrow assembly. In the absence of annexin A2, the small GTPase RhoA—which regulates cortical cytoskeletal rearrangement—fails to form a compact ring at the equatorial plane. Furthermore, annexin A2 is required for cortical localization of the RhoGEF Ect2 and to maintain the association between the equatorial cortex and the central spindle. Our results demonstrate that annexin A2 is necessary in the early phase of cytokinesis. We propose that annexin A2 participates in central spindle–equatorial plasma membrane communication. 相似文献
999.
1000.
Brown AD Bunnage ME Glossop PA James K Jones R Lane CA Lewthwaite RA Mantell S Perros-Huguet C Price DA Trevethick M Webster R 《Bioorganic & medicinal chemistry letters》2007,17(14):4012-4015
The design and profile of a series of saligenin containing long acting beta(2)-adrenoreceptor agonists is described. Evaluation of these analogues using a guinea-pig tissue model demonstrates that analogues within this series have significantly longer durations of action than salmeterol and have the potential for a once daily profile in human. 相似文献