Abstract
The duplication and stability of a eukaryotic chromosome requires the function of multiple spatially distributed DNA replication origins. The chromosomal positions of MCM complexes determine where origins can function. While the biochemistry of MCM complex assembly onto DNA, or origin licensing, is defined, it is unclear how the chromosomal distribution of MCM complexes is achieved. We have elucidated a role for the Sir2 histone deacetylase in establishing the normal distribution of MCM complexes over Saccharomyces cerevisiae chromosomes. In the absence of Sir2, MCM complexes accumulated within early replicating euchromatin, which enhanced origin activity within these regions at the expense of late replicating euchromatin; thus late replicating euchromatin remained unduplicated at the end of S-phase. We conclude that Sir2-mediated attenuation of MCM complex assembly within regions of the genome most receptive to origin licensing is necessary for the normal spatial distribution of MCM complexes and efficient duplication of yeast chromosomes.