Nanoelectromechanics of methylated DNA in a synthetic nanopore.
Methylation of cytosine is a covalent modification of DNA that can be used to silence genes, orchestrating a myriad of biological processes including cancer. We have discovered that a synthetic nanopore in a membrane comparable in thickness to a protein binding site can be used to detect methylation. We observe a voltage threshold for permeation of methylated DNA through a <2 nm diameter pore, which we attribute to the stretching transition; this can differ by >1 V/20 nm depending on the methylation level, but not the DNA sequence.
Mirsaidov
U
U
Timp
W
W
Zou
X
X
Dimitrov
V
V
Schulten
K
K
Feinberg
A P
AP
Timp
G
G
D000465:Algorithms; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D019175:DNA Methylation; D004587:Electrophoresis, Agar Gel; D019398:Genes, BRCA1; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008567:Membranes, Artificial; D010539:Permeability; D016133:Polymerase Chain Reaction; D011487:Protein Conformation
D008567:Membranes, Artificial; D007335:Insulin-Like Growth Factor II; D004247:DNA