Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Cell Commun Signal ; 17(1): 150, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744505
2.
Biochim Biophys Acta Gene Regul Mech ; 1862(9): 194408, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31382053

RESUMO

In Saccharomyces cerevisiae, Core Factor (CF) is a key evolutionarily conserved transcription initiation factor that helps recruit RNA polymerase I (Pol I) to the ribosomal DNA (rDNA) promoter. Upregulated Pol I transcription has been linked to many cancers, and targeting Pol I is an attractive and emerging anti-cancer strategy. Using yeast as a model system, we characterized how CF binds to the Pol I promoter by electrophoretic mobility shift assays (EMSA). Synthetic DNA competitors along with anti-tumor drugs and nucleic acid stains that act as DNA groove blockers were used to discover the binding preference of yeast CF. Our results show that CF employs a unique binding mechanism where it prefers the GC-rich minor groove within the rDNA promoter. In addition, we show that yeast CF is able to bind to the human rDNA promoter sequence that is divergent in DNA sequence and demonstrate CF sensitivity to the human specific Pol I inhibitor, CX-5461. Finally, we show that the human Core Promoter Element (CPE) can functionally replace the yeast Core Element (CE) in vivo when aligned by conserved DNA structural features rather than DNA sequence. Together, these findings suggest that the yeast CF and the human ortholog Selectivity Factor 1 (SL1) use an evolutionarily conserved, structure-based mechanism to target DNA. Their shared mechanism may offer a new avenue in using yeast to explore current and future Pol I anti-cancer compounds.


Assuntos
DNA Ribossômico/genética , RNA Polimerase I/genética , Fatores de Transcrição/genética , Transcrição Gênica , Benzotiazóis/farmacologia , Sequência Conservada/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Humanos , Naftiridinas/farmacologia , Conformação de Ácido Nucleico/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , RNA Polimerase I/química , Saccharomyces cerevisiae/genética , Fatores de Transcrição/química
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa