There are rings...

The DNA polymerase III holoenzyme, which carries out chromosomal DNA replication in Escherichia coli, comprises three main parts: the catalytic core, responsible for DNA synthesis; the doughnut-shaped sliding clamp (a head-to-tail dimer of β-subunits), which confers processivity; and the clamp-loading (or γ) complex, that consists principally of the γ-, δ- and δ'-subunits. The clamp-loading complex binds to and opens the β-clamp, which allows it to encircle the duplex DNA, and these authors have investigated how it does this by solving the crystal structures of a complex between the δ-subunit and the β-ring, and also of the entire γ-complex.

The authors propose that the mechanism by which the β?δ interaction leads to opening of the β-ring involves two components: first, the δ subunit acts as wrench, preventing the β-ring from closing; and second, the ring-opening mechanism is 'spring loaded' (the curvature of the β-monomer in the β?δ complex is reduced relative to within the β-dimer), supplementing the action of the δ-wrench.

The structure of the γ-complex uncovers a further twist. The subunits are arranged as a pentamer, with the stoichiometry δ':γ3:δ. This asymmetric arrangement, say the authors, might support a mechanism in which the γ-complex switches between two forms ? a 'closed' state, in which the δ-subunit is prevented from interacting with the β-clamp by δ'; and an 'open' state, in which δ is free to engage the β-ring.

References Mechanism of processivity clamp opening by the delta subunit wrench of the clamp loader complex of E. coli DNA polymerase III. Jeruzalmi, D. et al. Cell 106, 417-428 (2001)[PubMed]. Crystal structure of the processivity clamp loader gamma (g) complex of E. coli DNA polymerase III. Jeruzalmi, D., O'Donnell, M. & Kuriyan, J. Cell 106, 429?441 (2001) [PubMed]

...and rings

Twenty per cent of clinically relevant mutations in the BRCA1 tumour suppressor occur within the amino terminus. This region harbours a RING domain, through which BRCA1 interacts with other proteins, including BARD1. Brzovic et al. now report the solution structure of the heterodimer between the BRCA1?BARD1 RING domains (pictured). A comparison of this RING?RING interaction with that seen between two RAG1 homodimers shows the structural diversity of the interactions between different RING domains.

At the carboxyl terminus of BRCA1 is found the BRCT region, which is essential for the function of the protein in DNA repair and transcription. Williams et al. have solved the crystal structure of this region and mapped mutations that predispose to cancer onto the structure. They show that the BRCT domain contains two BRCT repeats that are arranged in a head-to-tail fashion. Mutations occur at the interface of these repeats, hence destabilizing the structure.

References  Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. Brzovic, P. S. et al. Nature Struct. Biol. 8, 833-837 (2001) [Contents page]. Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1. Williams, R. S., Green, R. & Glover, J. N. M. Nature Struct. Biol. 8, 838?842 (2001) [Contents page]