No abstract

Ellipticine is a natural plant product that has been found to be a powerful anticancer drug. Although still unclear, its mechanism of action is considered to be mainly based on DNA intercalation and/or the inhibition of topoisomerase II. Many experimental data suggest an intercalation based on stacking interactions along the major base‐pair axis, but alternative binding modes have been proposed, in particular for ellipticine derivatives. The 1.5 Å resolution structure of ellipticine complexed to a 6 bp oligonucleotide unveils its mode of binding and enables a detailed analysis of the distorting effects of the drug on the DNA.

PhoB is a two-component response regulator that activates transcription by interacting with the r 70 subunit of the E. coli RNA polymerase in promoters in which the À35 r 70 -recognition element is replaced by the pho box. The crystal structure of a transcription initiation subcomplex that includes the r 4 domain of r 70 fused with the RNA polymerase b subunit flap tip helix, the PhoB effector domain and the pho box DNA reveals how r 4 recognizes the upstream pho box repeat. As with the À35 element, r 4 achieves this recognition through the N-terminal portion of its DNA recognition helix, but contact with the DNA major groove is less extensive. Unexpectedly, the same recognition helix contacts the transactivation loop and helices a2 and a3 of PhoB. This result shows a simple and elegant mechanism for polymerase recruitment to pho box promoters in which the lost À35 element contacts are compensated by new ones with the activator. In addition, r 4 is reoriented, thereby suggesting a remodelling mechanism for transcription initiation.