ATPase switches controlling DNA replication initiation

Proteins that bind and hydrolyze ATP are frequently involved in the early s teps of DNA replication. Recent studies of Saccharomyces cerevisiae suggest that two members of the AAA+ ATPase family - the origin recognition comple x and Cdc6p - have separable roles for ATP binding and ATP hydrolysis durin g eukaryotic DNA replication. Intriguingly, the proposed regulation of thes e eukaryotic replication proteins by ATP has functional similarities to the ATP-dependent control of the DnaA and DnaC initiation factors from Escheri chia coli. Comparison of the ATP regulation of these factors suggests that ATP binding and hydrolysis acts as a molecular switch that couples key even ts during initiation of replication. This switch results in a significant c hange in protein function.