the major and minor grooves

Run your finger along a twisted rope or a candy cane and you feel a spiral groove. The DNA double helix has grooves too, and because its two backbones are not evenly spaced around the spiral, the grooves come in two sizes — a wide major groove and a narrow minor groove. These grooves are where proteins read the DNA without ever opening it.

As the two antiparallel strands twist around each other, the backbones run closer together on one side and farther apart on the other, carving two helical channels of unequal width that spiral down the molecule: the broad major groove and the slimmer minor groove. The edges of the base pairs face into these grooves, and crucially, the chemical pattern presented in the wide major groove differs for each base pair (A-T versus T-A versus G-C versus C-G). That pattern is a kind of Braille a protein can feel.

The grooves matter because they are how the cell reads a gene's sequence from the outside. A protein such as a transcription factor inserts part of itself — often a small helix — into the major groove and reads the exposed edges of the bases, recognising a specific sequence without unzipping the strands. Most sequence-specific DNA-binding proteins work this way, so the grooves are the reading surface on which gene regulation is built.