STRUCTURAL BIOLOGY: Getting DNA to Unwind

The initial step in duplicating a cellular genome is the unwinding of a limited region of double-stranded DNA to form a small single-stranded DNA bubble (see the figure) (1). In bacteria, archaea, and lower eukaryotes, the unwinding process begins at a sequence called the replication origin, which contains several conserved binding sites for a protein called the initiator. Binding of the initiator results in a nucleoprotein complex that "melts" DNA, forming the DNA bubble into which the replication machinery assembles. The architecture of the initiator-origin DNA nucleoprotein complex is largely unknown, but reports by Gaudier et al. on page 1213 (2) and by Dueber et al. on page 1210 (3) of this issue solve high-resolution structures of archaean initiator protein-origin DNA complexes that reveal several unexpected and novel features of initiator protein function.