English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/124720
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

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

AuthorsBrank, Adam S.; Güimil García, Ramón; Eritja Casadellà, Ramón ; Márquez, Víctor E.; Christman, Judith K.
KeywordsDNA methyltransferase
Epigenetics
Gene activation
Methylation inhibitor
5-azacytidine
Issue Date2002
PublisherAcademic Press
CitationJournal of Molecular Biology
AbstractThe 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.
Publisher version (URL)DOI: 10.1016/S0022-2836(02)00918-X
URIhttp://hdl.handle.net/10261/124720
DOI10.1016/S0022-2836(02)00918-X
Appears in Collections:(IQAC) Artículos
Files in This Item:
File Description SizeFormat 
JMB2002.pdfArtículo principal786,81 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.