Functional asymmetry in processivity clamp proteins.

Abstract

Symmetric homo-oligomeric proteins comprising multiple copies of identical subunits are abundant in all domains of life. To fulfill their biological function, these complexes undergo conformational changes, binding events, or post-translational modifications leading to loss of symmetry. Processivity clamp proteins that encircle DNA and play multiple roles in DNA replication and repair are archetypical homo-oligomeric symmetric protein complexes. The symmetrical nature of processivity clamps enables simultaneous interactions with multiple protein binding partners; such interactions result in asymmetric changes that facilitate the transition between clamp loading and DNA replication, and between DNA replication and repair. The ring-shaped processivity clamps are opened and loaded onto DNA by clamp-loader complexes via asymmetric intermediates with one of the intermonomer interfaces disrupted, undergo spontaneous opening events, and bind heterogeneous partners. Eukaryotic clamp proteins are subject to ubiquitylation, SUMOylation, and acetylation affecting their biological functions. There is increasing evidence of the functional asymmetry of the processivity clamp proteins from structural, biophysical, and computational studies. Here, we review the symmetry and asymmetry of processivity clamps and their roles in regulating the various functions of the clamps.