Rotation of a DNA nucleotide out of the double helix and into a protein binding pocket ('base flipping') was first observed in the structure of a DNA methyltransferase. There is now evidence that a variety of proteins use base flipping in their interactions with DNA. Though the mechanism for base flipping is still unclear, we propose a three-step pathway: recognizing the target site and increasing the interstrand phosphate-phosphate distance nearby, initiating base flipping by protein invasion of the DNA, and trapping the flipped DNA structure. © Current Biology Ltd.
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