Slip Slidin' Along - How DNA Binding Proteins Find Their Target

Many proteins bind to double-stranded DNA and most of them bind specifically to a particular target site. The lac repressor, for example, binds to a specific DNA site that blocks transcription of the genes required for lactose uptake and utilization. The lac repressor protein is a dimer of two identical subunits and each one binds a short segment with the core sequence ATTGT.¹

If you look closely at the structure shown above, you can see how parts of the protein lie in the grove of double-stranded DNA where they can detect the sequence by "reading" the chemical groups on the edges of the base pairs. It's important to realize that DNA binding proteins interact with the DNA double helix and not with unwound DNA where the individual bases are exposed.

How does a DNA binding protein like lac repressor find its specific site in the genome? The most obvious explanation is that the protein binds non-specifically to any piece of DNA and checks to see if it's a specific binding site. If it is, the protein binds very tightly and doesn't fall off. If it isn't, the interaction is much weaker and the protein falls off quickly so it can check out another potential site.

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