908 resultados para BRCA1, DNA damage, genome stability, DNA repair, mRNA splicing


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Phytochemical investigation of Chioccoca alba afforded three new iridoids, alboside I, alboside II and alboside III, and a new seco-iridoid alboside V. Alboside IV showed moderate activity towards the DNA repair-deficient mutant RS321 of Saccharomyces cerevisiae. The structural elucidation of the new compounds was performed by ES-MS and by 1D and 2D NMR spectroscopic methods. (C) 1999 Elsevier B.V. Ltd. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Bioactivity-guided fractionation of a methanolic CHCl 3 extract of the leaves of Pterogyne nitens afforded the known guanidine alkaloid pterogynidine [2] and three new guanidine alkaloids, nitensidines A [3], B [4], and C [5], all of which exhibited selective activity towards the DNA repair-deficient yeast mutant RS 321 (IC 12=9.3-20.0 μg/ml); 3,4, and 5 were moderately cytotoxic to CHO Aux B 1 cells (IC 50=8.5-13.0 μg/ml).

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Pós-graduação em Ciências Biológicas (Genética) - IBB

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A Chromobacterium violaceum é uma beta-proteobactéria Gram-negativa comum da microbiota tropical e um patógeno oportunista para animais e humanos. A infecção causada pela C. violaceum apresenta alta taxa de mortalidade, mas os mecanismos da patogenicidade ainda não foram caracterizados. Como outros microorganismos ambientais, essa bactéria está exposta a condições externas muito variáveis, que exigem grande adaptabilidade e sistemas de proteção eficientes. Entre esses sistemas encontra-se um operon arsRBC de resistência ao arsênio, metaloide danoso à saúde humana associado a lesões de pele, doenças neurológicas e câncer. O objetivo deste trabalho foi investigar as alterações na expressão proteica de C. violaceum ATCC 12472 na presença do arsenito e caracterizar as diversas proteínas secretadas pela bactéria. As proteínas da C. violaceum foram analisadas por eletroforese bidimensional e espectrometria de massas. A análise proteômica revelou que o arsenito induz um aumento na quantidade das proteínas envolvidas na resposta ao estresse oxidativo, reparo do DNA e metabolismo energético. Entre as proteínas secretadas, foram identificados fatores de virulência (metalopeptidases, colagenase e toxinas), transportadores, proteínas de proteção contra estresses e com potencial aplicação biotecnológica. Os resultados mostraram que a C. violaceum possui um arsenal molecular de adaptação que a torna capaz de conservar suas atividades celulares e provocar lesões em outros organismos.

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Aberrant methylation of CpG islands located in promoter regions represents one of the major mechanisms for silencing cancer-related genes in tumor cells. We determined the frequency of aberrant CpG island methylation for several tumor-associated genes: DAPK, MGMT, p14ARF, p16INK4a, TP73, RB1 and TIMP-3 in 55 brain tumors, consisting of 26 neuroepithelial tumors, 6 peripheral nerve tumors, 13 meningeal tumors and 10 metastatic brain tumors. Aberrant methylation of at least one of the seven genes studied was detected in 83.6% of the cases. The frequencies of aberrant methylation were: 40% for p14ARF, 38.2% for MGMT, 30.9% for, p16INK4a, 14.6% for TP73 and for TIMP-3, 12.7% for DAPK and 1.8% for RB1. These data suggest that the hypermethylation observed in the genes p14ARF, MGMT and p16INK4a is a very important event in the formation or progression of brain tumors, since the inactivation of these genes directly interferes with the cell cycle or DNA repair. The altered methylation rate of the other genes has already been reported to be related to tumorigenesis, but the low methylation rate of RB1 found in tumors in our sample is different from that so far reported in the literature, suggesting that perhaps hypermethylation of the promoter is not the main event in the inactivation of this gene. Our results suggest that hypermethylation of the promoter region is a very common event in nervous system tumors.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Micronuclei (MN) originate from chromosome fragments or whole chromosomes that lag behind at anaphase during cell division can occur due to excessive exposure to harmful agents, defects in mitosis and / or DNA repair process. The study evaluated the frequency of micronuclei in cytological samples after daily use of alcohol -based mouthwash mouth in smokers and non-smokers. We assessed 30 subjects, aged between 17-42 years and established as exclusion criteria: alcohol consumption; periodontal disease; systemic diseases that may interfere with the integrity of the oral mucosa; individuals with medical or pharmacological history that affect the performance of the study, family history of malignancies. For smokers the inclusion criterion was a minimum consumption of 20 cigarettes / day, and the contrast required for non-smokers. The sample was divided into 02 experimental groups: Group 1 Smokers and Group 2 Non-Smokers, both groups performed mouthwash (alcohol 21,6%) with Listerine® Defense of Teeth and Gums for 04 weeks cytological collection were performed on buccal mucosa and portion median border of the tongue, one for initial, week 0 control, and subsequent three weeks with continued use of mouthwash. The collected material was stained by specific staining Feulgen / Fast Green. The analysis of 3000 cells / individual was performed by light microscopy statistics used Kruskal- Wallis and Mann-Whitney tests for frequency MN. The frequency of micronuclei in buccal mucosa was 1.6 ± 1.75 and 1.46 ± 2.06 for the site language to Group 1 Smokers of showing a slight increase compared with Group 2 Non-smoking, which showed a variation of 1.2 ± 1.53 for the buccal mucosa site and 0.86 ± 1.41 for the site language. However, this difference was not statistically significant. The results suggest that alcohol-based mouthwash tested is not an inducer of genotoxic changes, thus not changing the frequency...

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Among extremophiles, microorganisms resistant to ultraviolet radiation (UVR) have been known to produce a variety of metabolites (i.e., extremolytes). We hypothesized that natural microbial flora on elevated land (hills) would reveal a variety of UVR-resistant extremophiles and polyextremophiles with modulated proteins and enzymes that had biotechnological implications. Microorganisms Cellulosimicrobium cellulans UVP1 and Bacillus pumilus UVP4 were isolated and identified using 16S rRNA sequencing, and showed extreme UV resistance (1.03 x 106 and 1.71 x 105 similar to J/m2, respectively) from elevated land soil samples along with unique patterns of protein expression under UVR and non-UVR. A broad range of cellulolytic activity on carboxymethyl cellulose agar plates in C. cellulans UVP1 and B. pumilus UVP4 was revealed at varying pH, temperature, and inorganic salt concentration. Further, the microbial strain B. pumilus UVP4 showed the basic characteristics of a novel group: polyextremophiles with significance in bioenergy.