English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/124720
Compartir / Impacto:
Estadísticas
Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Título

Inhibition of Hha I DNA (cytosine-c5) methyltransferase by oligodeoxyribonucleotides containing 5-Aza-2′-deoxycytidine: Examination of the intertwined roles of co-factor, target, transition state structure and enzyme conformation

AutorBrank, Adam S.; Güimil García, Ramón; Eritja Casadellà, Ramón; Márquez, Víctor E.; Christman, Judith K.
Palabras claveDNA methyltransferase
Epigenetics
Gene activation
Methylation inhibitor
5-azacytidine
Fecha de publicación2002
EditorAcademic Press
CitaciónJournal of Molecular Biology
ResumenThe presence of 5-azacytosine (ZCyt) residues in DNA leads to potent inhibition of DNA (cytosine-C5) methyltranferases (C5-MTases) in vivo and in vitro. Enzymatic methylation of cytosine in mammalian DNA is an epigenetic modification that can alter gene activity and chromosomal stability, influencing both differentiation and tumorigenesis. Thus, it is important to understand the critical mechanistic determinants of ZCyt's inhibitory action. Although several DNA C5-MTases have been reported to undergo essentially irreversible binding to ZCyt in DNA, there is little agreement as to the role of AdoMet and/or methyl transfer in stabilizing enzyme interactions with ZCyt. Our results demonstrate that formation of stable complexes between Hha I methyltransferase (M.Hha I) and oligo-deoxyribonucleotides containing ZCyt at the target position for methylation (ZCyt-ODNs) occurs in both the absence and presence of co-factors, AdoMet and AdoHcy. Both binary and ternary complexes survive SDS-PAGE under reducing conditions and take on a compact conformation that increases their electrophoretic mobility in comparison to free M.Hha I. Since methyl transfer can occur only in the presence of AdoMet, these results suggest (1) that the inhibitory capacity of ZCyt in DNA is based on its ability to induce a stable, tightly closed conformation of M.Hha I that prevents DNA and co-factor release and (2) that methylation of ZCyt in DNA is not required for inhibition of M.Hha I.
Versión del editorDOI: 10.1016/S0022-2836(02)00918-X
URIhttp://hdl.handle.net/10261/124720
DOI10.1016/S0022-2836(02)00918-X
Aparece en las colecciones: (IQAC) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
JMB2002.pdfArtículo principal786,81 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.