Origin selection articles from across Nature Portfolio

A protocol for quantitative genome-wide detection of replication initiation, fork progression and termination, based on purification and strand-specific sequencing of Okazaki fragments isolated from mammalian or yeast cells.

Most eukaryotes do not use a consensus DNA sequence as binding sites for the origin recognition complex (ORC) to initiate DNA replication, however budding yeast do. Here the authors show S. cerevisiae ORC can bind nucleosomes near nucleosome-free regions and recruit replicative helicases to form a pre-replication complex independent of the DNA sequence.

The range of available copy numbers for cloning vectors is largely restricted to the handful of ORIs that have been isolated from plasmids found in nature. Here the authors introduce a plasmid system that allow for the continuous, finely-tuned control of plasmid copy number between 1 and 800 copies per cell.

A study shows that the three-dimensional conformation of the human genome influences the positioning of DNA replication initiation zones, highlighting cohesin-mediated loop anchors as essential determinants of their precise location.

Cryo-EM structures of S. cerevisiae ORC bound to DNA and Cdc6 reveal an autoinhibited conformation and suggest a mechanism of origin licensing control in response to CDK phosphorylation.