Structural insights into Cdc45 function: was there a nuclease at the heart of the ancestral replisome?

The role of Cdc45 in genomic duplication has remained unclear since its initial identification as an essential replication factor. Recent structural studies of Cdc45 and the evolutionarily-related archaeal GAN and bacterial RecJ nucleases have provided fresh insight into its function as co-activator of the MCM helicase. The CMG helicase of the last archaeal/eukaryotic ancestor might have harboured a single-stranded DNA nuclease activity, conserved in some modern archaea.Work in the author's laboratory described in this article was funded by a Wellcome Trust investigator award (104641/Z/14/Z)