Eukaryotic
In eukaryotes, the budding yeast Saccharomyces cerevisiae has the best characterised replication origins. These origins were first identified by their ability to support the replication of mini-chromosomes or plasmids, giving rise to the name Autonomously replicating sequences or ARS elements. Each budding yeast origin consists of a short (~11 bp) essential DNA sequence (called the ARS consensus sequence or ACS) that recruits replication proteins.
In other eukaryotes, including humans, the DNA sequences at the replication origins vary. Despite this sequence variation, all the origins form a base for assembly of a group of proteins known collectively as the pre-replication complex (pre-RC):
- First, the origin DNA is bound by the Origin Recognition Complex (ORC) which, with help from two further protein factors (Cdc6 and Cdt1), load the Mini Chromosome Maintenance (or MCM) protein complex.
- Once assembled, this complex of proteins indicates that the replication origin is ready for activation. Once the replication origin is activated, the cell's DNA will be replicated.
In metazoans, pre-RC formation is inhibited by the protein Geminin, which binds to and inactivates Cdt1. Regulation of replication, such as this, is important as it prevents the DNA from being replicated more than once each cell cycle.
In humans an origin of replication has been originally identified near the Lamin B2 gene on chromosome 19 and the ORC bindig to it has extensively been studied.
Read more about this topic: Origin Of Replication