Nucleotides choose origins

In vertebrate cells, not all potential DNA replication origins fire in each S phase, but it is unclear what parameters control that decision. Mauro Anglana, Michelle Debatisse (Institut Curie, Paris, France), and colleagues find that nucleotide availability can determine which origins are activated.

Under normal conditions (when nucleotides were readily available), initiation occurred predominantly at one site within the AMPD2 locus. Only in a few cases did minor sites fire instead. Firing of the dominant origin seems to prevent other nearby origins from initiating replication, as only an origin spaced far from the major origin was used simultaneously.

Cells with limited nucleotide availability, however, replicated from a wider variety of origins. Although the predominant origin was not used as often, simultaneous activation from multiple minor sites was more common. Firing efficiency of competent origins has been...