DNA replication origins

Cold Spring Harb Perspect Biol. 2013 Oct 1;5(10):a010116. doi: 10.1101/cshperspect.a010116.

Abstract

The onset of genomic DNA synthesis requires precise interactions of specialized initiator proteins with DNA at sites where the replication machinery can be loaded. These sites, defined as replication origins, are found at a few unique locations in all of the prokaryotic chromosomes examined so far. However, replication origins are dispersed among tens of thousands of loci in metazoan chromosomes, thereby raising questions regarding the role of specific nucleotide sequences and chromatin environment in origin selection and the mechanisms used by initiators to recognize replication origins. Close examination of bacterial and archaeal replication origins reveals an array of DNA sequence motifs that position individual initiator protein molecules and promote initiator oligomerization on origin DNA. Conversely, the need for specific recognition sequences in eukaryotic replication origins is relaxed. In fact, the primary rule for origin selection appears to be flexibility, a feature that is modulated either by structural elements or by epigenetic mechanisms at least partly linked to the organization of the genome for gene expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Archaea / genetics
  • Bacteria / genetics
  • Binding Sites
  • Chromatin / metabolism
  • DNA Replication / physiology*
  • Drosophila / genetics
  • Models, Genetic*
  • Origin Recognition Complex / genetics
  • Replication Origin*
  • Saccharomyces cerevisiae / genetics*
  • Yeasts / genetics

Substances

  • Chromatin
  • Origin Recognition Complex