Evolutionary clues to eukaryotic DNA clamp-loading mechanisms: analysis of the functional constraints imposed on replication factor C AAA+ ATPases.

ABSTRACT: Ring-shaped sliding clamps encircle DNA and bind to DNA polymerase, thereby preventing it from falling off during DNA replication. In eukaryotes, sliding clamps are loaded onto DNA by the replication factor C (RFC) complex, which consists of five distinct subunits (A-E), each of which contains an AAA+ module composed of a RecA-like alpha/beta ATPase domain followed by a helical domain. AAA+ ATPases mediate chaperone-like protein remodeling. Despite remarkable progress in our understanding of clamp loaders, it is still unclear how recognition of primed DNA by RFC triggers ATP hydrolysis and how hydrolysis leads to conformational changes that can load the clamp onto DNA. While these questions can, of course, only be resolved experimentally, the design of such experiments is itself non-trivia

SUBMITTER: Neuwald AF 

PROVIDER: S-EPMC1160110 | biostudies-literature | 2005

REPOSITORIES: biostudies-literature