Selection of replication initiation sites

Eukaryotes, such as yeast and people, have large genomes with millions of bases encoding the genetic information. To ensure complete replication of these genomes within the allowed time, the process of DNA replication starts at multiple sites along each chromosome, called replication origins. These replication origins are specialised DNA sequences that assemble the cellular machinery that then moves along the DNA, reading and copying the genetic material.

DNA replication starts at specific location called replication origins. To complete DNA replication within S phase, replication of eukaryotic genomes is initiated at multiple discrete chromosomal sites called replication origins; the yeast genome contains hundreds of origins and the human genome contains thousands. Replication is controlled primarily by the regulated activation of origins. Replication origins activate at characteristic times during S phase to produce bi-directional replication forks that progress to replicate the flanking DNA.
Replication origin sites are sequence determined by the binding specificity of ORC and nucleosome positioning around potential ORC-binding sites. In budding yeast, ORC recognises a specific sequence motif that is non- transcribed and in a nucleosome-depleted region. Metazoan ORC is also recruited to non-transcribed and nucleosome-depleted regions, although with little sequence specificity. Therefore, budding yeasts offer a powerful system: defined and manipulatable origins that recruit the conserved eukaryotic replication machinery to chromatin contexts similar to metazoans.

Related publications

From sequence to function: Insights from natural variation in budding yeasts.
Nieduszynski & Liti (2011)
Biochim. Biophys. Acta, 1810(10):959-66

The origin recognition complex interacts with a subset of metabolic genes tightly linked to origins of replication.
Shor et al. (2009)
PLoS Genet., 5(12):e1000755

Genome-wide identification of replication origins in yeast by comparative genomics.
Nieduszynski et al. (2006)
Genes Dev., 20(14):1874-9

Further publications