Stalling of human methyltransferase at single-strand conformers from the Huntington's locus.

We describe evidence for a sequence of events in which the Human DNA(cytosine-5)methyl-transferase first methylates spontaneous single-stranded conformers (SSCs) and then stalls at the methylated site to produce a complex with the conformationally unusual DNA. This property of the enzyme is a result of its ability to respond to a general loss of symmetry at its CG recognition site. The data suggest that DNA methyltransferase, itself, may physically participate in biological processes that distinguish between DNA that is in the normal Watson-Crick paired conformation and DNA that is conformationally unusual (e.g. a hairpin loop or misassembled replication intermediate). The in vitro methylation of spontaneous SSCs from the Huntington's locus illustrates the phenomenon.