Untying DNA knots

Structural biologists at the Friedrich Miescher Institute for Biomedical Research have resolved the 3D structure of a protein machine that plays an important part in the maintenance of genomic stability. They have revealed how one unit of the machine, RMI, modulates the workings of an enzyme, topoisomerase III? (TopIII?), thus allowing double Holliday junctions - key intermediates in DNA repair - to be disentangled. Their results have been published in Nature Structural & Molecular Biology. The dissolvasome, as its name suggests, helps to remove otherwise harmful DNA intermediates by untying structural knots - so-called double Holliday junctions - that arise during DNA replication and repair. It is composed of three central proteins - a topoisomerase (TopIII?), which relieves topological stress in DNA; BLM, a strand-separating helicase; and RMI1, a small helper protein. Mutations in any of the dissolvasome subunits result in gross chromosomal instability, but it has not been clear how the protein machine's components work together to catalyze the untangling of DNA knots. The group led by Nicolas Thomä at the Friedrich Miescher Institute for Biomedical Research has now resolved the 3D structure of RMI bound to human TopIII? and shown how RMI modulates the activity of the dissolvasome.