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  1 / 27 MEDLINE  
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[PMID]:28678401
[Au] Autor:Chandrasekharappa SC; Chinn SB; Donovan FX; Chowdhury NI; Kamat A; Adeyemo AA; Thomas JW; Vemulapalli M; Hussey CS; Reid HH; Mullikin JC; Wei Q; Sturgis EM
[Ad] Endereço:Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
[Ti] Título:Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50.
[So] Source:Cancer;123(20):3943-3954, 2017 Oct 15.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Patients with Fanconi anemia (FA) have an increased risk for head and neck squamous cell carcinoma (HNSCC). The authors sought to determine the prevalence of undiagnosed FA and FA carriers among patients with HNSCC as well as an age cutoff for FA genetic screening. METHODS: Germline DNA samples from 417 patients with HNSCC aged <50 years were screened for sequence variants by targeted next-generation sequencing of the entire length of 16 FA genes. RESULTS: The sequence revealed 194 FA gene variants in 185 patients (44%). The variant spectrum was comprised of 183 nonsynonymous point mutations, 9 indels, 1 large deletion, and 1 synonymous variant that was predicted to effect splicing. One hundred eight patients (26%) had at least 1 rare variant that was predicted to be damaging, and 57 (14%) had at least 1 rare variant that was predicted to be damaging and had been previously reported. Fifteen patients carried 2 rare variants or an X-linked variant in an FA gene. Overall, an age cutoff for FA screening was not identified among young patients with HNSCC, because there were no significant differences in mutation rates when patients were stratified by age, tumor site, ethnicity, smoking status, or human papillomavirus status. However, an increased burden, or mutation load, of FA gene variants was observed in carriers of the genes FA complementation group D2 (FANCD2), FANCE, and FANCL in the HNSCC patient cohort relative to the 1000 Genomes population. CONCLUSIONS: FA germline functional variants offer a novel area of study in HNSCC tumorigenesis. FANCE and FANCL, which are components of the core complex, are known to be responsible for the recruitment and ubiquitination, respectively, of FANCD2, a critical step in the FA DNA repair pathway. In the current cohort, the increased mutation load of FANCD2, FANCE, and FANCL variants among younger patients with HNSCC indicates the importance of the FA pathway in HNSCC. Cancer 2017;123:3943-54. © 2017 American Cancer Society.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/genética
Anemia de Fanconi/genética
Neoplasias de Cabeça e Pescoço/genética
[Mh] Termos MeSH secundário: Adulto
Idade de Início
Proteína BRCA2/genética
Análise Mutacional de DNA
Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética
Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
Proteína do Grupo de Complementação L da Anemia de Fanconi/genética
Proteínas de Grupos de Complementação da Anemia de Fanconi/genética
Feminino
Mutação em Linhagem Germinativa
Heterozigoto
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Masculino
Meia-Idade
Polimorfismo de Nucleotídeo Único
Recombinases/genética
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BRCA2 Protein); 0 (BRCA2 protein, human); 0 (FANCD2 protein, human); 0 (FANCE protein, human); 0 (FANCI protein, human); 0 (Fanconi Anemia Complementation Group D2 Protein); 0 (Fanconi Anemia Complementation Group E Protein); 0 (Fanconi Anemia Complementation Group Proteins); 0 (Recombinases); EC 2.3.2.27 (FANCL protein, human); EC 2.3.2.27 (Fanconi Anemia Complementation Group L Protein); EC 3.1.- (SLX4 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170706
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30802


  2 / 27 MEDLINE  
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[PMID]:27986371
[Au] Autor:van Twest S; Murphy VJ; Hodson C; Tan W; Swuec P; O'Rourke JJ; Heierhorst J; Crismani W; Deans AJ
[Ad] Endereço:Genome Stability Unit, St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia.
[Ti] Título:Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway.
[So] Source:Mol Cell;65(2):247-259, 2017 Jan 19.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monoubiquitination and deubiquitination of FANCD2:FANCI heterodimer is central to DNA repair in a pathway that is defective in the cancer predisposition syndrome Fanconi anemia (FA). The "FA core complex" contains the RING-E3 ligase FANCL and seven other essential proteins that are mutated in various FA subtypes. Here, we purified recombinant FA core complex to reveal the function of these other proteins. The complex contains two spatially separate FANCL molecules that are dimerized by FANCB and FAAP100. FANCC and FANCE act as substrate receptors and restrict monoubiquitination to the FANCD2:FANCI heterodimer in only a DNA-bound form. FANCA and FANCG are dispensable for maximal in vitro ubiquitination. Finally, we show that the reversal of this reaction by the USP1:UAF1 deubiquitinase only occurs when DNA is disengaged. Our work reveals the mechanistic basis for temporal and spatial control of FANCD2:FANCI monoubiquitination that is critical for chemotherapy responses and prevention of Fanconi anemia.
[Mh] Termos MeSH primário: Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo
Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo
Anemia de Fanconi/metabolismo
Ubiquitinação
[Mh] Termos MeSH secundário: Linhagem Celular
DNA/genética
DNA/metabolismo
Proteínas de Ligação a DNA/metabolismo
Anemia de Fanconi/genética
Proteína do Grupo de Complementação A da Anemia de Fanconi/metabolismo
Proteína do Grupo de Complementação C da Anemia de Fanconi/metabolismo
Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética
Proteína do Grupo de Complementação E da Anemia de Fanconi/metabolismo
Proteína do Grupo de Complementação G da Anemia de Fanconi/metabolismo
Proteína do Grupo de Complementação L da Anemia de Fanconi/metabolismo
Proteínas de Grupos de Complementação da Anemia de Fanconi/genética
Seres Humanos
Proteína 2 Inibidora de Diferenciação/metabolismo
Complexos Multiproteicos
Proteínas Nucleares/metabolismo
Ligação Proteica
Multimerização Proteica
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
Fatores de Tempo
Transfecção
Proteases Específicas de Ubiquitina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (FAAP100 protein, human); 0 (FANCA protein, human); 0 (FANCB protein, human); 0 (FANCC protein, human); 0 (FANCD2 protein, human); 0 (FANCE protein, human); 0 (FANCG protein, human); 0 (FANCI protein, human); 0 (Fanconi Anemia Complementation Group A Protein); 0 (Fanconi Anemia Complementation Group C Protein); 0 (Fanconi Anemia Complementation Group D2 Protein); 0 (Fanconi Anemia Complementation Group E Protein); 0 (Fanconi Anemia Complementation Group G Protein); 0 (Fanconi Anemia Complementation Group Proteins); 0 (ID2 protein, human); 0 (Inhibitor of Differentiation Protein 2); 0 (Multiprotein Complexes); 0 (Nuclear Proteins); 0 (Recombinant Proteins); 0 (USP1 associated factor 1, human); 9007-49-2 (DNA); EC 2.3.2.27 (FANCL protein, human); EC 2.3.2.27 (Fanconi Anemia Complementation Group L Protein); EC 3.4.19.12 (USP1 protein, human); EC 3.4.19.12 (Ubiquitin-Specific Proteases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161218
[St] Status:MEDLINE


  3 / 27 MEDLINE  
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[PMID]:27994462
[Au] Autor:Yu J; Zhang J; Xing H; Sun Y; Yang Z; Yang T; Cai C; Zhao X; Yang L; Ding P
[Ad] Endereço:School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
[Ti] Título:Novel guanidinylated bioresponsive poly(amidoamine)s designed for short hairpin RNA delivery.
[So] Source:Int J Nanomedicine;11:6651-6666, 2016.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Two different disulfide (SS)-containing poly(amidoamine) (PAA) polymers were constructed using guanidino (Gua)-containing monomers (ie, arginine [Arg] and agmatine [Agm]) and , '-cystamine bisacrylamide (CBA) by Michael-addition polymerization. In order to characterize these two Gua-SS-PAA polymers and investigate their potentials as short hairpin RNA (shRNA)-delivery carriers, pSilencer 4.1-CMV shRNA was chosen as a model plasmid DNA to form complexes with these two polymers. The Gua-SS-PAAs and plasmid DNA complexes were determined with particle sizes less than 90 nm and positive ζ-potentials under 20 mV at nucleic acid:polymer weight ratios lower than 1:24. Bioresponsive release of plasmid DNA was observed from both newly constructed complexes. Significantly lower cytotoxicity was observed for both polymer complexes compared with polyethylenimine and Lipofectamine 2000, two widely used transfection reagents as reference carriers. Arg-CBA showed higher transfection efficiency and gene-silencing efficiency in MCF7 cells than Agm-CBA and the reference carriers. In addition, the cellular uptake of Arg-CBA in MCF7 cells was found to be higher and faster than Agm-CBA and the reference carriers. Similarly, plasmid DNA transport into the nucleus mediated by Arg-CBA was more than that by Agm-CBA and the reference carriers. The study suggested that guanidine and carboxyl introduced into Gua-SS-PAAs polymers resulted in a better nuclear localization effect, which played a key role in the observed enhancement of transfection efficiency and low cytotoxicity. Overall, two newly synthesized Gua-SS-PAAs polymers demonstrated great potential to be used as shRNA carriers for gene-therapy applications.
[Mh] Termos MeSH primário: Sobrevivência Celular/efeitos dos fármacos
Proteína do Grupo de Complementação E da Anemia de Fanconi/antagonistas & inibidores
Plasmídeos/administração & dosagem
Poliaminas/química
Polímeros/química
RNA Interferente Pequeno/administração & dosagem
[Mh] Termos MeSH secundário: DNA/genética
Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
Seres Humanos
Células MCF-7
Microscopia de Força Atômica
Tamanho da Partícula
Plasmídeos/química
Polietilenoimina
Polimerização
RNA Interferente Pequeno/química
RNA Interferente Pequeno/genética
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (FANCE protein, human); 0 (Fanconi Anemia Complementation Group E Protein); 0 (Poly(amidoamine)); 0 (Polyamines); 0 (Polymers); 0 (RNA, Small Interfering); 9002-98-6 (Polyethyleneimine); 9007-49-2 (DNA)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170224
[Lr] Data última revisão:
170224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161221
[St] Status:MEDLINE


  4 / 27 MEDLINE  
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[PMID]:27486799
[Au] Autor:Fu C; Begum K; Jordan PW; He Y; Overbeek PA
[Ad] Endereço:Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
[Ti] Título:Dearth and Delayed Maturation of Testicular Germ Cells in Fanconi Anemia E Mutant Male Mice.
[So] Source:PLoS One;11(8):e0159800, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:After using a self-inactivating lentivirus for non-targeted insertional mutagenesis in mice, we identified a transgenic family with a recessive mutation that resulted in reduced fertility in homozygous transgenic mice. The lentiviral integration site was amplified by inverse PCR. Sequencing revealed that integration had occurred in intron 8 of the mouse Fance gene, which encodes the Fanconi anemia E (Fance) protein. Fanconi anemia (FA) proteins play pivotal roles in cellular responses to DNA damage and Fance acts as a molecular bridge between the FA core complex and Fancd2. To investigate the reduced fertility in the mutant males, we analyzed postnatal development of testicular germ cells. At one week after birth, most tubules in the mutant testes contained few or no germ cells. Over the next 2-3 weeks, germ cells accumulated in a limited number of tubules, so that some tubules contained germ cells around the full periphery of the tubule. Once sufficient numbers of germ cells had accumulated, they began to undergo the later stages of spermatogenesis. Immunoassays revealed that the Fancd2 protein accumulated around the periphery of the nucleus in normal developing spermatocytes, but we did not detect a similar localization of Fancd2 in the Fance mutant testes. Our assays indicate that although Fance mutant males are germ cell deficient at birth, the extant germ cells can proliferate and, if they reach a threshold density, can differentiate into mature sperm. Analogous to previous studies of FA genes in mice, our results show that the Fance protein plays an important, but not absolutely essential, role in the initial developmental expansion of the male germ line.
[Mh] Termos MeSH primário: Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
Infertilidade Masculina/genética
Maturação do Esperma
Espermatozoides/fisiologia
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Diferenciação Celular
Proliferação Celular
Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo
Infertilidade Masculina/metabolismo
Íntrons
Masculino
Camundongos
Camundongos Transgênicos
Mutagênese Insercional
Túbulos Seminíferos/ultraestrutura
Espermatogênese
Espermatozoides/citologia
Espermatozoides/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fancd2 protein, mouse); 0 (Fance protein, mouse); 0 (Fanconi Anemia Complementation Group D2 Protein); 0 (Fanconi Anemia Complementation Group E Protein)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160804
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0159800


  5 / 27 MEDLINE  
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[PMID]:27165003
[Au] Autor:Esteban-Jurado C; Franch-Expósito S; Muñoz J; Ocaña T; Carballal S; López-Cerón M; Cuatrecasas M; Vila-Casadesús M; Lozano JJ; Serra E; Beltran S; Brea-Fernández A; Ruiz-Ponte C; Castells A; Bujanda L; Garre P; Caldés T; Cubiella J; Balaguer F; Castellví-Bel S
[Ad] Endereço:Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
[Ti] Título:The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer.
[So] Source:Eur J Hum Genet;24(10):1501-5, 2016 Oct.
[Is] ISSN:1476-5438
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Colorectal cancer (CRC) is one of the most common neoplasms in the world. Fanconi anemia (FA) is a very rare genetic disease causing bone marrow failure, congenital growth abnormalities and cancer predisposition. The comprehensive FA DNA damage repair pathway requires the collaboration of 53 proteins and it is necessary to restore genome integrity by efficiently repairing damaged DNA. A link between FA genes in breast and ovarian cancer germline predisposition has been previously suggested. We selected 74 CRC patients from 40 unrelated Spanish families with strong CRC aggregation compatible with an autosomal dominant pattern of inheritance and without mutations in known hereditary CRC genes and performed germline DNA whole-exome sequencing with the aim of finding new candidate germline predisposition variants. After sequencing and data analysis, variant prioritization selected only those very rare alterations, producing a putative loss of function and located in genes with a role compatible with cancer. We detected an enrichment for variants in FA DNA damage repair pathway genes in our familial CRC cohort as 6 families carried heterozygous, rare, potentially pathogenic variants located in BRCA2/FANCD1, BRIP1/FANCJ, FANCC, FANCE and REV3L/POLZ. In conclusion, the FA DNA damage repair pathway may play an important role in the inherited predisposition to CRC.
[Mh] Termos MeSH primário: Neoplasias Colorretais/genética
Reparo do DNA/genética
Anemia de Fanconi/genética
Predisposição Genética para Doença
Mutação em Linhagem Germinativa
[Mh] Termos MeSH secundário: Proteína BRCA1/genética
Neoplasias Colorretais/epidemiologia
Neoplasias Colorretais/patologia
Proteínas de Ligação a DNA/genética
DNA Polimerase Dirigida por DNA/genética
Exoma
Anemia de Fanconi/epidemiologia
Anemia de Fanconi/patologia
Proteína do Grupo de Complementação C da Anemia de Fanconi/genética
Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
Feminino
Genes Dominantes
Seres Humanos
Masculino
Linhagem
Espanha
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BRCA1 Protein); 0 (BRCA1 protein, human); 0 (DNA-Binding Proteins); 0 (FANCC protein, human); 0 (FANCE protein, human); 0 (Fanconi Anemia Complementation Group C Protein); 0 (Fanconi Anemia Complementation Group E Protein); EC 2.7.7.7 (DNA-Directed DNA Polymerase); EC 2.7.7.7 (REV3L protein, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170616
[Lr] Data última revisão:
170616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160512
[St] Status:MEDLINE
[do] DOI:10.1038/ejhg.2016.44


  6 / 27 MEDLINE  
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[PMID]:26939056
[Au] Autor:Fu C; Begum K; Overbeek PA
[Ad] Endereço:Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
[Ti] Título:Primary Ovarian Insufficiency Induced by Fanconi Anemia E Mutation in a Mouse Model.
[So] Source:PLoS One;11(3):e0144285, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In most cases of primary ovarian insufficiency (POI), the cause of the depletion of ovarian follicles is unknown. Fanconi anemia (FA) proteins are known to play important roles in follicular development. Using random insertional mutagenesis with a lentiviral transgene, we identified a family with reduced fertility in the homozygous transgenic mice. We identified the integration site and found that the lentivirus had integrated into intron 8 of the Fanconi E gene (Fance). By RT-PCR and in situ hybridization, we found that Fance transcript levels were significantly reduced. The Fance homozygous mutant mice were assayed for changes in ovarian development, follicle numbers and estrous cycle. Ovarian dysplasias and a severe lack of follicles were seen in the mutant mice. In addition, the estrous cycle was disrupted in adult females. Our results suggest that POI has been induced by the Fance mutation in this new mouse model.
[Mh] Termos MeSH primário: Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
Anemia de Fanconi/genética
Mutação
Folículo Ovariano/metabolismo
Insuficiência Ovariana Primária/genética
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Ciclo Estral/genética
Anemia de Fanconi/complicações
Anemia de Fanconi/metabolismo
Anemia de Fanconi/patologia
Proteína do Grupo de Complementação E da Anemia de Fanconi/deficiência
Feminino
Vetores Genéticos
Homozigoto
Seres Humanos
Hibridização In Situ
Íntrons
Lentivirus/genética
Camundongos
Mutagênese Insercional
Folículo Ovariano/patologia
Insuficiência Ovariana Primária/complicações
Insuficiência Ovariana Primária/metabolismo
Insuficiência Ovariana Primária/patologia
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Transcrição Genética
Transgenes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fanconi Anemia Complementation Group E Protein)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160311
[Lr] Data última revisão:
160311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160304
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0144285


  7 / 27 MEDLINE  
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[PMID]:26277624
[Au] Autor:Bouffard F; Plourde K; Bélanger S; Ouellette G; Labrie Y; Durocher F
[Ad] Endereço:CHU de Québec Research Centre and Laval University, Québec City, QC, Canada G1V 4G2.
[Ti] Título:Analysis of a FANCE Splice Isoform in Regard to DNA Repair.
[So] Source:J Mol Biol;427(19):3056-73, 2015 Sep 25.
[Is] ISSN:1089-8638
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The FANC-BRCA DNA repair pathway is activated in response to interstrand crosslinks formed in DNA. A homozygous mutation in 1 of the 17 Fanconi anemia (FA) genes results in malfunctions of this pathway and development of FA syndrome. The integrity of this protein network is essential for good maintenance of DNA repair process and genome stability. Following the identification of an alternatively splice isoform of FANCE (Fanconi anemia complementation group E) significantly expressed in breast cancer individuals from high-risk non-BRCA1/2 families, we studied the impact of this FANCE splice isoform (FANCEΔ4) on DNA repair processes. We have demonstrated that FANCEΔ4 mRNA was efficiently translated into a functional protein and expressed in normal and breast cancer cell lines. Following treatment with the crosslinking agent mitomycin C, EUFA130 (FANCE-deficient) cells infected with FANCEΔ4 were blocked into G2/M phase, while cell survival was significantly reduced compared with FANCE-infected EUFA130 cells. In addition, FANCEΔ4 did not allow FANCD2 and FANCI monoubiquitination, which represents a crucial step of the FANC-BRCA functional pathway. As observed for FANCE wild-type protein, localization of FANCEΔ4 protein was confined to the nucleus following mitomycin C treatment. Although FANCEΔ4 protein showed interaction with FANCE, FANCEΔ4 did not support normal function of FANCE protein in this pathway and could have deleterious effects on FANCE protein activity. We have demonstrated that FANCEΔ4 seems to act as a regulator of FANCD2 protein expression level by promoting its degradation. This study highlights the importance of an efficient regulation of alternative splicing expression of FA genes for proper DNA repair.
[Mh] Termos MeSH primário: Processamento Alternativo
Reparo do DNA
Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
Anemia de Fanconi/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteína BRCA1/metabolismo
Proteína BRCA2/metabolismo
Sobrevivência Celular
Anemia de Fanconi/metabolismo
Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética
Proteína do Grupo de Complementação E da Anemia de Fanconi/química
Proteína do Grupo de Complementação E da Anemia de Fanconi/metabolismo
Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo
Regulação da Expressão Gênica
Células HEK293
Seres Humanos
Modelos Moleculares
Dados de Sequência Molecular
Isoformas de Proteínas/química
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Estrutura Terciária de Proteína
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (BRCA1 Protein); 0 (BRCA2 Protein); 0 (Fanconi Anemia Complementation Group D2 Protein); 0 (Fanconi Anemia Complementation Group E Protein); 0 (Fanconi Anemia Complementation Group Proteins); 0 (Protein Isoforms)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:150921
[Lr] Data última revisão:
150921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150817
[St] Status:MEDLINE


  8 / 27 MEDLINE  
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[PMID]:24451376
[Au] Autor:Polito D; Cukras S; Wang X; Spence P; Moreau L; D'Andrea AD; Kee Y
[Ad] Endereço:From the Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, Florida 33620.
[Ti] Título:The carboxyl terminus of FANCE recruits FANCD2 to the Fanconi Anemia (FA) E3 ligase complex to promote the FA DNA repair pathway.
[So] Source:J Biol Chem;289(10):7003-10, 2014 Mar 07.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fanconi anemia (FA) is a genome instability syndrome characterized by bone marrow failure and cellular hypersensitivity to DNA cross-linking agents. In response to DNA damage, the FA pathway is activated through the cooperation of 16 FA proteins. A central player in the pathway is a multisubunit E3 ubiquitin ligase complex or the FA core complex, which monoubiquitinates its substrates FANCD2 and FANCI. FANCE, a subunit of the FA core complex, plays an essential role by promoting the integrity of the complex and by directly recognizing FANCD2. To delineate its role in substrate ubiquitination from the core complex assembly, we analyzed a series of mutations within FANCE. We report that a phenylalanine located at the highly conserved extreme C terminus, referred to as Phe-522, is a critical residue for mediating the monoubiquitination of the FANCD2-FANCI complex. Using the FANCE mutant that specifically disrupts the FANCE-FANCD2 interaction as a tool, we found that the interaction-deficient mutant conferred cellular sensitivity in reconstituted FANCE-deficient cells to a similar degree as FANCE null cells, suggesting the significance of the FANCE-FANCD2 interaction in promoting cisplatin resistance. Intriguingly, ectopic expression of the FANCE C terminus fragment alone in FA normal cells disrupts DNA repair, consolidating the importance of the FANCE-FANCD2 interaction in the DNA cross-link repair.
[Mh] Termos MeSH primário: Reparo do DNA
Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo
Proteína do Grupo de Complementação E da Anemia de Fanconi/metabolismo
Anemia de Fanconi/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Anemia de Fanconi/genética
Proteína do Grupo de Complementação E da Anemia de Fanconi/química
Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
Proteína do Grupo de Complementação L da Anemia de Fanconi/metabolismo
Células HEK293
Células HeLa
Seres Humanos
Dados de Sequência Molecular
Fenilalanina/química
Fenilalanina/genética
Fenilalanina/metabolismo
Estrutura Terciária de Proteína
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fanconi Anemia Complementation Group D2 Protein); 0 (Fanconi Anemia Complementation Group E Protein); 47E5O17Y3R (Phenylalanine); EC 2.3.2.27 (Fanconi Anemia Complementation Group L Protein); EC 2.3.2.27 (Ubiquitin-Protein Ligases)
[Em] Mês de entrada:1406
[Cu] Atualização por classe:161207
[Lr] Data última revisão:
161207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140124
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M113.533976


  9 / 27 MEDLINE  
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[PMID]:24185200
[Au] Autor:Seuter S; Pehkonen P; Heikkinen S; Carlberg C
[Ad] Endereço:School of Medicine, Institute of Biomedicine, University of Eastern Finland, FIN-70211 Kuopio, Finland.
[Ti] Título:Dynamics of 1α,25-dihydroxyvitamin D3-dependent chromatin accessibility of early vitamin D receptor target genes.
[So] Source:Biochim Biophys Acta;1829(12):1266-75, 2013 Dec.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The signaling cascade of the transcription factor vitamin D receptor (VDR) is triggered by its specific ligand 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). In this study we demonstrate that in THP-1 human monocytic leukemia cells 87.4% of the 1034 most prominent genome-wide VDR binding sites co-localize with loci of open chromatin. At 165 of them 1α,25(OH)2D3 strongly increases chromatin accessibility and has at further 217 sites weaker effects. Interestingly, VDR binding sites in 1α,25(OH)2D3-responsive chromatin regions are far more often composed of direct repeats with 3 intervening nucleotides (DR3s) than those in ligand insensitive regions. DR3-containing VDR sites are enriched in the neighborhood of genes that are involved in controling cellular growth, while non-DR3 VDR binding is often found close to genes related to immunity. At the example of six early VDR target genes we show that the slope of their 1α,25(OH)2D3-induced transcription correlates with the basal chromatin accessibility of their major VDR binding regions. However, the chromatin loci controlling these genes are indistinguishable in their VDR association kinetics. Taken together, ligand responsive chromatin loci represent dynamically regulated contact points of VDR with the genome, from where it controls early 1α,25(OH)2D3 target genes.
[Mh] Termos MeSH primário: Cromatina/genética
Leucemia Monocítica Aguda/genética
Receptores de Calcitriol/genética
Sequências Repetitivas de Ácido Nucleico/genética
Vitamina D/análogos & derivados
[Mh] Termos MeSH secundário: Acetilação
Western Blotting
Imunoprecipitação da Cromatina
Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
Fator de Crescimento Semelhante a EGF de Ligação à Heparina
Inibidores de Histona Desacetilases/farmacologia
Seres Humanos
Peptídeos e Proteínas de Sinalização Intercelular/genética
Leucemia Monocítica Aguda/tratamento farmacológico
Receptores de Lipopolissacarídeos/genética
Subunidade p50 de NF-kappa B/genética
Proteína 2 Ligante de Morte Celular Programada 1/genética
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Receptores de Calcitriol/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Células Tumorais Cultivadas
Vitamina D/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromatin); 0 (FANCE protein, human); 0 (Fanconi Anemia Complementation Group E Protein); 0 (HBEGF protein, human); 0 (Heparin-binding EGF-like Growth Factor); 0 (Histone Deacetylase Inhibitors); 0 (Intercellular Signaling Peptides and Proteins); 0 (Lipopolysaccharide Receptors); 0 (NF-kappa B p50 Subunit); 0 (NFKB1 protein, human); 0 (PDCD1LG2 protein, human); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (RNA, Messenger); 0 (Receptors, Calcitriol); 0 (dihydroxy-vitamin D3); 1406-16-2 (Vitamin D)
[Em] Mês de entrada:1402
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131105
[St] Status:MEDLINE


  10 / 27 MEDLINE  
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[PMID]:21826217
[Au] Autor:Meier D; Schindler D
[Ad] Endereço:Department of Human Genetics, University of Wurzburg, Wurzburg, Germany. daniel.meier@biozentrum.uni-wuerzburg.de
[Ti] Título:Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.
[So] Source:PLoS One;6(8):e22911, 2011.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-ß and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.
[Mh] Termos MeSH primário: Regiões Promotoras Genéticas/genética
Elementos Reguladores de Transcrição/genética
[Mh] Termos MeSH secundário: Sítios de Ligação
DNA Helicases/genética
Ensaio de Desvio de Mobilidade Eletroforética
Anemia de Fanconi/genética
Proteína do Grupo de Complementação A da Anemia de Fanconi/genética
Proteína do Grupo de Complementação C da Anemia de Fanconi/genética
Proteína do Grupo de Complementação E da Anemia de Fanconi/genética
Proteína do Grupo de Complementação F da Anemia de Fanconi/genética
Proteína do Grupo de Complementação G da Anemia de Fanconi/genética
Proteína do Grupo de Complementação L da Anemia de Fanconi/genética
Proteínas de Grupos de Complementação da Anemia de Fanconi/genética
Células HEK293
Células HeLa
Seres Humanos
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Fator de Crescimento Transformador beta
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (FANCA protein, human); 0 (FANCB protein, human); 0 (FANCC protein, human); 0 (FANCE protein, human); 0 (FANCF protein, human); 0 (FANCG protein, human); 0 (Fanconi Anemia Complementation Group A Protein); 0 (Fanconi Anemia Complementation Group C Protein); 0 (Fanconi Anemia Complementation Group E Protein); 0 (Fanconi Anemia Complementation Group F Protein); 0 (Fanconi Anemia Complementation Group G Protein); 0 (Fanconi Anemia Complementation Group Proteins); 0 (Transcription Factors); 0 (Transforming Growth Factor beta); EC 2.3.2.27 (FANCL protein, human); EC 2.3.2.27 (Fanconi Anemia Complementation Group L Protein); EC 3.6.1.- (FANCM protein, human); EC 3.6.4.- (DNA Helicases)
[Em] Mês de entrada:1112
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110810
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0022911



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