Timothy Hoggard, Allison J Hollatz, Rachel E Cherney, Melissa R Seman, and Catherine A Fox
Nucleic Acids Research, gkab450, doi: 10.1093/nar/gkab450
The distribution of DNA replication origins across eukaryotic chromosomes is important for the replication of the genome and for genetic stability. The identity of sites in the yeast genome from which replication initiates has been known for many years, yet whether additional cis-acting sequences influence the ORC binding step, the first step of the origin cycle, is unclear. Here, the investigators employed genomic, genetic, molecular and computational experiments to discover that the conserved Fkh1 transcription factor promotes binding of chromosomal DNA by ORC at a subset of DNA replication origins. Previous data established that the functional ORC binding step occurs in G1-phase. In contrast, while it is known that Fkh1 can regulate origin activity in yeast, previously published mechanistic models support a view of Fkh1 regulation as occurring at origin activation, or the S-phase step in the origin cycle. This study defines a new mechanism by which Fkh1 can regulate origin activity.