SYNERGY BETWEEN ADJACENT ZINC FINGERS IN SEQUENCE-SPECIFIC DNA RECOGNITION

Zif268-like zinc fingers are generally regarded as independent DNA-bin ding modules that each specify three base pairs in adjacent, but discr ete, subsites, However, crystallographic evidence suggests that a cont act also can occur from the second helical position of one finger to t he subsite of the preceding finger, Here we show for the three-finger DNA-binding domain of the protein Zif268, and a panel of variants, tha t deleting the putative contact from finger 3 can affect the binding s pecificity for the 5' base in the adjoining triplet, which forms part of the binding site of finger 2, This finding demonstrates that Zif268 -like zinc fingers can specify overlapping 4-bp suhsites, and that seq uence specificity at the boundary between subsites arises from synergy between adjacent fingers. This has important implications for the des ign and selection of zinc fingers with novel DNA binding specificities .