Hormones trigger dramatic changes in the structure and transcriptional activity of specific promoters that lead to exchange of repression complexes for activation complexes. Ju et al. (2006) now show that estrogen-dependent restructuring and transcription of the pS2 promoter require the generation of a DNA double-strand break by a novel protein complex containing two enzymes, topoisomerase IIβ and poly(ADP-ribose) polymerase.