Specification of DNA Replication Origins and Genomic Base Composition in Fission Yeasts Review Article

In the “Replicon Theory”, Jacob, Brenner and Cuzin proposed the existence of replicators and initiators as the two major actors in DNA replication. Over the years, many protein components of initiators have been shown to be conserved in different organisms during evolution. By contrast, replicator DNA sequences (often referred to as replication origins) have diverged beyond possible comparison between eukaryotic genomes. Replication origins in the fission yeast Schizosaccharomyces pombe are made up of A + T-rich sequences that do not share any consensus elements. The information encoded in these replicators is interpreted by the Orc4 subunit of the ORC (origin recognition complex), which is unique among eukaryotes in that it contains a large domain harboring nine AT-hook subdomains that target ORC to a great variety of A + T-rich sequences along the chromosomes. Recently, the genomes of other Schizosaccharomyces species have been sequenced and the regions encompassing their replication origins have been identified. DNA sequence analysis and comparison of the organization of their Orc4 proteins have revealed species-specific differences that contribute to our understanding of how the specification of replication origins has evolved during the phylogenetic divergence of fission yeasts.