Efficient duplication of the genome and its equal distribution into both daughter cells is an essential process for all dividing organisms. To ensure that DNA replication occurs only once during the S phase of the cell cycle, initiation of replication is tightly controlled. Initiation factors are responsible for the recruitment of the replisome, the large molecular machine carrying out DNA synthesis, to origins of replication and license them to start DNA duplication. Remarkably, most of the currently known initiators have been classified as members of the family of AAA(+) ATPases. In our recent study we identified an additional AAA(+) ATPase, CDC-48, to be essential for proper DNA replication in Caenorhabditis elegans. Here, we speculate on the function of CDC-48 (also known as Cdc48p in yeast and p97 in vertebrates) during DNA replication initiation, addressing its ubiquitin-selective chaperone activity.
