Regulation of Replication Origins

  • Anna B. Marks
  • Haiqing Fu
  • Mirit I. AladjemEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1042)


In eukaryotes, genome duplication starts concomitantly at many replication initiation sites termed replication origins. The replication initiation program is spatially and temporally coordinated to ensure accurate, efficient DNA synthesis that duplicates the entire genome while maintaining other chromatin-dependent functions. Unlike in prokaryotes, not all potential replication origins in eukaryotes are needed for complete genome duplication during each cell cycle. Instead, eukaryotic cells vary the use of initiation sites so that only a fraction of potential replication origins initiate replication each cell cycle. Flexibility in origin choice allows each eukaryotic cell type to utilize different initiation sites, corresponding to unique nuclear DNA packaging patterns. These patterns coordinate replication with gene expression and chromatin condensation. Budding yeast replication origins share a consensus sequence that marks potential initiation sites. Metazoan origins, on the other hand, lack a consensus sequence. Rather, they are associated with a collection of structural features, chromatin packaging features, histone modifications, transcription, and DNA-DNA/DNA-protein interactions. These features confer cell type-specific replication and expression and play an essential role in maintaining genomic stability.


DNA replication Cell cycle regulation Replication origin licensing Chromatin organization Histone modification Replication timing 


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© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Developmental Therapeutics BranchCenter for Cancer Research, NCI, NIHBethesdaUSA

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