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151.
Katherine N Choe Claudia M Nicolae Daniel Constantin Yuka Imamura Kawasawa Maria Rocio Delgado‐Diaz Subhajyoti De Raimundo Freire Veronique AJ Smits George‐Lucian Moldovan 《EMBO reports》2016,17(6):874-886
Defects in DNA replication, DNA damage response, and DNA repair compromise genomic stability and promote cancer development. In particular, unrepaired DNA lesions can arrest the progression of the DNA replication machinery during S‐phase, causing replication stress, mutations, and DNA breaks. HUWE1 is a HECT‐type ubiquitin ligase that targets proteins involved in cell fate, survival, and differentiation. Here, we report that HUWE1 is essential for genomic stability, by promoting replication of damaged DNA. We show that HUWE1‐knockout cells are unable to mitigate replication stress, resulting in replication defects and DNA breakage. Importantly, we find that this novel role of HUWE1 requires its interaction with the replication factor PCNA, a master regulator of replication fork restart, at stalled replication forks. Finally, we provide evidence that HUWE1 mono‐ubiquitinates H2AX to promote signaling at stalled forks. Altogether, our work identifies HUWE1 as a novel regulator of the replication stress response. 相似文献
152.
Rocio Sanchez-Alcudia Maria Garcia-Hoyos Miguel Angel Lopez-Martinez Noelia Sanchez-Bolivar Olga Zurita Ascension Gimenez Cristina Villaverde Luciana Rodrigues-Jacy da Silva Marta Corton Raquel Perez-Carro Simona Torriano Vasiliki Kalatzis Carlo Rivolta Almudena Avila-Fernandez Isabel Lorda Maria J. Trujillo-Tiebas Blanca Garcia-Sandoval Maria Isabel Lopez-Molina Fiona Blanco-Kelly Rosa Riveiro-Alvarez Carmen Ayuso 《PloS one》2016,11(4)
Choroideremia (CHM) is a rare X-linked disease leading to progressive retinal degeneration resulting in blindness. The disorder is caused by mutations in the CHM gene encoding REP-1 protein, an essential component of the Rab geranylgeranyltransferase (GGTase) complex. In the present study, we evaluated a multi-technique analysis algorithm to describe the mutational spectrum identified in a large cohort of cases and further correlate CHM variants with phenotypic characteristics and biochemical defects of choroideremia patients. Molecular genetic testing led to the characterization of 36 out of 45 unrelated CHM families (80%), allowing the clinical reclassification of four CHM families. Haplotype reconstruction showed independent origins for the recurrent p.Arg293* and p.Lys178Argfs*5 mutations, suggesting the presence of hotspots in CHM, as well as the identification of two different unrelated events involving exon 9 deletion. No certain genotype-phenotype correlation could be established. Furthermore, all the patients´ fibroblasts analyzed presented significantly increased levels of unprenylated Rabs proteins compared to control cells; however, this was not related to the genotype. This research demonstrates the major potential of the algorithm proposed for diagnosis. Our data enhance the importance of establish a differential diagnosis with other retinal dystrophies, supporting the idea of an underestimated prevalence of choroideremia. Moreover, they suggested that the severity of the disorder cannot be exclusively explained by the genotype. 相似文献
153.
Emma M. Brown Gordon J. McDougall Derek Stewart Gema Pereira-Caro Rocio González-Barrio Philip Allsopp Pamela Magee Alan Crozier Ian Rowland Chris I. R. Gill 《PloS one》2012,7(11)
Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer. 相似文献
154.
Ralf Horbach Aura Rocio Navarro-QuesadaWolfgang Knogge Holger B. Deising 《Journal of plant physiology》2011,168(1):51-62
Fungi cause severe diseases on a broad range of crop and ornamental plants, leading to significant economical losses. Plant pathogenic fungi exhibit a huge variability in their mode of infection, differentiation and function of infection structures and nutritional strategy. In this review, advances in understanding mechanisms of biotrophy, necrotrophy and hemibiotrophic lifestyles are described. Special emphasis is given to the biotrophy-necrotrophy switch of hemibiotrophic pathogens, and to biosynthesis, chemical diversity and mode of action of various fungal toxins produced during the infection process. 相似文献
155.
156.
Rocio Mateo-Gallego Maria Solanas-Barca Elena Burillo Ana Cenarro Iva Marques-Lopes Fernando Civeira 《Journal of physiology and biochemistry》2010,66(3):229-236
Iron deposits are associated with lipid phenotype in familial hypertriglyceridemias, mainly familial combined hyperlipidemia
(FCH) and familial hypertriglyceridemia (FHTG). In turn, diet plays an important role in hypertriglyceridemias although it
is not known if dietary patterns are associated with iron concentration in these disorders. The objective was to determine
the relationship between diet and iron deposits, measured through serum ferritin concentration, in patients with FCH and FHTG.
The study was composed of 140 patients, 107 with FCH and 33 with FHTG. Subjects completed a validated 137-item food frequency
questionnaire. Dividing subjects by ferritin tertiles adjusted by sex, there were no significant differences in dietary patterns
except in dairy products consumption which was lower in the highest ferritin tertile. Subjects were also divided by triglycerides
tertiles adjusted by sex. Those subjects in the highest tertile had lower HDL cholesterol and higher ferritin concentrations.
Regarding to dietary parameters, there were significant differences in marine omega three fatty acids and vegetables presenting
higher and lower consumption, respectively, those patients in the highest tertile of triglycerides. Moreover, there was not
a significant correlation between dietary iron intake and any parameter, both biochemical and dietary, including ferritin
concentrations. In conclusion, in patients with primary hypertriglyceridemia, triglycerides are associated with ferritin concentrations
but dietary patterns are not related to iron deposits. Our results highly support the concept that the genetic mechanisms
driven to hypertriglyceridemia also favor iron overload. 相似文献
157.
Rocio J. Alcántara-Hernández Carla M. Centeno Alejandro Ponce-Mendoza Silvia Batista Martin Merino-Ibarra Julio Campo Luisa I. Falcón 《Polar Biology》2014,37(3):403-416
Cyanobacterial microbial mats are highly structured communities commonly found in Antarctic inland waters including melt streams. These benthic microbial associations comprise a large number of microorganisms with different metabolic capacities, impacting nutrient dynamics where established. The denitrification process is a feasible nitrogen loss pathway and a biological source of nitrous oxide, a potent greenhouse gas that also promotes ozone depletion. Potential denitrifiers from five microbial mats were characterized using a PCR-DGGE (denaturing gradient gel electrophoresis) approach. Molecular markers encoding for key enzymes in the denitrification process (nirK, nirS and nosZ) were used. Fingerprints were obtained for the five sampled mats and compared for two successive years. Distance analysis showed that despite the sampled year, the denitrifying genetic potential was similar between most of the sites when represented in Euclidean space. The number of dominant denitrifiers detected for each sample ranged between 6 and 18 for nirK, 4–10 for nirS and 6–17 for nosZ. The seventy-two sequenced phylotypes showed 80–98 % identity to previously reported environmental sequences from water column, sediments and soil samples. These results suggest that Antarctic microbial mats have a large denitrification potential, previously uncharacterized and composed by both site-specific and common phylotypes belonging mainly to Alpha-, Beta- and Gammaproteobacteria. 相似文献
158.
159.
160.
Rocio J. Alcántara-Hernández César Valenzuela-Encinas Rodolfo Marsch Luc Dendooven 《Extremophiles : life under extreme conditions》2009,13(1):169-178
The diversity of the dissimilatory and respiratory nitrate-reducing communities was studied in two soils of the former lake
Texcoco (Mexico). Genes encoding the membrane-bound nitrate reductase (narG) and the periplasmic nitrate reductase (napA) were used as functional markers. To investigate bacterial communities containing napA and narG in saline alkaline soils of the former lake Texcoco, libraries of the two sites were constructed (soil T3 with pH 11 and
electrolytic conductivity in saturated extract (ECSE) 160 dS m−1 and soil T1 with pH 8.5 and ECSE 0.8 dS m−1). Phylogenetic analysis of napA sequences separated the clone families into two main groups: dependent or independent of NapB. Most of napA sequences from site T1 were grouped in the NapB-dependent clade, meanwhile most of the napA sequences from the extreme soil T3 were affiliated to the NapB-independent group. For both sites, partial narG sequences were associated with representatives of the Proteobacteria, Firmicutes and Actinobacteria phyla, but the proportions of the clones were different. Our results support the concept of a specific and complex nitrate-reducing
community for each soil of the former lake Texcoco. 相似文献