The dynamic impact of CpG methylation in DNA.
Solid-state deuterium NMR is used to investigate perturbations of the local, internal dynamics in the EcoRI restriction binding site, -GAATTC- induced by cytidine methylation. Methylation of the cytidine base in this sequence is known to suppress hydrolysis by the EcoRI restriction enzyme. Previous solid-state deuterium NMR studies have detected large amplitude motions of the phosphate-sugar backbone at the AT-CG junction of the unmethylated DNA sequence. This study shows that methylation of the cytidine base in a CpG dinucleotide reduces the amplitudes of motions of the phosphate-sugar backbone. These observations suggest a direct link between suppression of the amplitudes of localized, internal motions of the sugar-phosphate backbone of the DNA and inhibition of restriction enzyme cleavage.
Geahigan
K B
KB
Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
Meints
G A
GA
Hatcher
M E
ME
Orban
J
J
Drobny
G P
GP
D001483:Base Sequence; D003198:Computer Simulation; D018899:CpG Islands / Q000235:genetics*; D003562:Cytidine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015246:Deoxyribonuclease EcoRI / Q000378:metabolism; D003903:Deuterium / Q000378:metabolism; D004058:Diffusion; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009038:Motion; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D003562:Cytidine; D004247:DNA; D003903:Deuterium; D015246:Deoxyribonuclease EcoRI