Dynamics of DNA replication in a eukaryotic cell

Abstract

Significance All eukaryotic cells initiate DNA replication at multiple genomic sites. For most cell types these sites lack a well-defined sequence signature, so it is not understood how they are selected. To analyze the factors that influence initiation site selection and determine the dynamics of replication throughout the genome, we developed an integrative computational model of DNA replication in the model organism Schizosaccharomyces pombe . This analysis showed that the locations of initiation sites are determined not only by the sequence preferences of the S. pombe origin recognition complex (ORC), but also by the interference of transcription with the formation of prereplication complexes. Our findings suggest that transcription has influenced evolution of the binding properties of ORC and replication dynamics in eukaryotes.