Origin of replication

The origin of replication (also called the replication origin) is a particular sequence in a genome at which replication is initiated.^[1] This can either be DNA replication in living organisms such as prokaryotes and eukaryotes, or RNA replication in RNA viruses, such as double-stranded RNA viruses. DNA replication may proceed from this point bidirectionally or unidirectionally.

The specific structure of the origin of replication varies somewhat from species to species, but all share some common characteristics such as high AT content. The origin of replication binds the pre-replication complex, a protein complex that recognizes, unwinds, and begins to copy DNA.

Types

The two types of replication origin are :

• Narrow or broad host range
• High- or low-copy number

There are also significant differences between prokaryotic and eukaryotic origins of replication:

• Bacteria have a single circular molecule of DNA, and typically only a single origin of replication per circular chromosome.^[2]
• Archaea have a single circular molecule of DNA, and several origins of replication along this circular chromosome.^[3]
• Eukaryotes often have multiple origins of replication on each linear chromosome, with up to 100,000 present in a single human cell.^[4] Having many origins of replication helps to speed the duplication of their (usually) much larger store of genetic material. The segment of DNA that is copied starting from each unique replication origin is called a replicon.

Origins of replication are typically assigned names containing ori.

Prokaryotic

The E. coli replication origin is known as oriC. In E. coli, the oriC consists of three A-T rich 13-mer repeats and four 9-mer repeats. Ten to 20 monomers of the replication protein dnaA bind to the 9 mer repeats, and the DNA coils around this protein complex forming a protein core. This coiling stimulates the AT rich region in the 13 mer sequence to unwind, allowing copies of the helicase dnaB and its cofactor protein dnaC to bind to each strand of the resulting single-stranded DNA. The dnaB protein forms the basis of the replisome, a complex of enzymes that performs DNA replication^[5].

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 replication more than once each cell cycle.

References

External links

• OriDB, the DNA Replication Origin Database
• Ori-Finder, an online software for prediction of bacterial and archaeal oriCs
• MeSH Replication+Origin

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