For the analysis of protein-DNA interactions by coupled gel-shift/foot
printing, DNA fragments need to be extracted from polyacrylamide gels
and subsequently separated on high resolution gels. Due to impurities
in the extracted DNA, single nucleotide resolution is frequently not a
chieved. We now describe an improved experimental strategy that employ
s transient coupling of DNA fragments to a solid support in order to e
xtract DNA of high purity quantitatively, rapidly and reliably. As an
example, we describe the application of our protocol to the 'in-gel fo
otprinting' by copper phenanthroline. The method should also find appl
ication to the chemical interference assays.