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.
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The two types of replication origin are :
There are also significant differences between prokaryotic and eukaryotic origins of replication:
Origins of replication are typically assigned names containing ori.
The genome of E. coli is contained in a single circular DNA molecule of 4.6 x 106 nucleotide pairs. DNA replication begins at a single origin of replication. 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]
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):
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.
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