In a zinc finger protein, certain sequences of amino acid residues are able to recognise and bind to an extended target-site of four or even five nucleotides[1] When this occurs in a ZFP in which the three-nucleotide subsites are contiguous, one zinc finger interferes with the target-site of the zinc finger adjacent to it, a situation known as target-site overlap.
The hydrogen bond between Asp2 and the N4 of either a cytosine or adenine base paired to the guanine or thymine, respectively defines these two nucleotides at the 3' position, defining a sequence that overlaps into the subsite of any zinc finger that may be attached N-terminally.
[2][3] Target-site overlap limits the modularity of those zinc fingers which exhibit it, by restricting the number of situations to which they can be applied.
[4] The extent to which target-site overlap occurs is largely unknown, with a variety of amino acids having shown involvement in such interactions.
[3] Since the problem only appears to occur in a limited number of cases, the issue is nullified in most situations in which there are a variety of suitable targets to choose from[2] and only becomes a real issue if binding to a specific DNA sequence is required (e.g. blocking binding by endogenous DNA-binding proteins).