The binding of lac repressor and the catabolite gene activator protein to halogen-substituted analogues of poly[d(A-T)].

We have measured the binding of two regulatory proteins to the complete halogen-substituted series of poly[d(A-T)] analogues. Both the lac repressor and the catabolite gene activator protein were found to bind more strongly to all of the halogen-substituted DNAs than they do to poly[d(A-T)]. For both proteins, the order of binding preference is poly[d(A-ioU)] is greater than poly[d(A-brU)] is greater than or equal to poly[d(A-clU)] is greater than poly[d(A-flU)] is greater than poly[d(A-T)]. Quantitative data on the binding of these proteins to poly[d(A-U)] is also given. The significance of these results for the mechanism of protein-DNA interaction is discussed. This is the first report that an activator protein binds more strongly to a halogen-substituted DNA; we discuss this result with regard to the mechanism of action of bromodeoxyruidine and other halogen-substituted base analogues on the inhibition and induction of differentiation in eucaryotic cells.