Choice of origins and replication timing control in budding yeast

Abstract

A complete and exact replication of every eukaryotic chromosome within each cell division cycle is essential to maintain stable genomes during cell proliferation. Abundant origins of DNA replication where the replication machinery assembles into replisomes to initiate DNA synthesis are widespread along chromosomes. DNA replication shows characteristic spatio-temporal patterns of origin usage and replication timing during S phase, which are conserved through evolution and are cell type specific, indicating an active process of regulation. Important advances have recently been made to elucidate the determinants and molecular mechanisms that regulate the patterns of origin activation. Among these, cis-acting elements, chromatin determinants, the timing of origin licensing and factors regulating the choice of origins and the firing timing during S phase have been described in Saccharomyces cerevisiae. Much less understood is the biological significance of this replication programme, but it could be significant in providing both robustness and plasticity to the DNA replication process in terms of replication completion and the maintenance of genome integrity.