Methyltransferase-Directed DNA Strand Scission

Abstract

We demonstrate here that MTase-modified DNA can undergo the Staudinger ligation with triarylphosphines derivatized with phenanthroline. Presentation of these duplexes with Cu(II) and 3-mercaptopropionic acid leads to strand scission proximal to the MTase recognition site. By virtue of their ability to use a synthetic azide-bearing cofactor, M.TaqI and M.HhaI produce a DNA lesion that induces scission 5' to the base modified by the enzyme. This chemistry represents a new approach by which regions of DNA methylation can be rapidly identified on the basis of DNA damage.