Origin of replication
Encyclopedia
The origin of replication (also called the replication origin) is a particular sequence in a genome
at which replication is initiated. This can either be DNA replication
in living organisms such as prokaryotes and eukaryotes, or RNA replication in RNA virus
es, 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.
There are also significant differences between prokaryotic and eukaryotic origins of replication:
Origins of replication are typically assigned names containing ori
.
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.
s 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
.
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
at which replication is initiated. This can either be DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
in living organisms such as prokaryotes and eukaryotes, or RNA replication in RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
es, such as double-stranded RNA viruses
Double-stranded RNA viruses
Double-stranded RNA viruses are a diverse group of viruses that vary widely in host range , genome segment number , and virion organization...
. 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
Pre-replication complex
A pre-replication complex is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will carry the...
, 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:
- BacteriaBacteriaBacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
have a single circular molecule of DNA, and typically only a single origin of replication per circular chromosome. - ArchaeaArchaeaThe Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
have a single circular molecule of DNA, and several origins of replication along this circular chromosome. - EukaryoteEukaryoteA eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s often have multiple origins of replication on each linear chromosome that initiate at different times (replication timingReplication timingReplication Timing refers to the order in which segments of DNA along the length of a chromosome are duplicated.-DNA Replication:In eukaryotic cells , chromosomes consist of very long linear double-stranded DNA molecules...
), with up to 100,000 present in a single human cell. 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 repliconReplicon (genetics)A replicon is a DNA molecule or RNA molecule, or a region of DNA or RNA, that replicates from a single origin of replication.For most prokaryotic chromosomes, the replicon is the entire chromosome. One notable exception found comes from archaea, where two Sulfolobus species have been shown to...
.
Origins of replication are typically assigned names containing ori
Ori (genetics)
Ori is the DNA sequence that signals for the origin of replication, sometimes referred to simply as origin. In E. coli, ori is some 250 nucleotides in length for the chromosomal origin...
.
Prokaryotic
The genome of E. coliEscherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
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
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
, the oriC consists of three A-T rich 13-mer
Repeat unit
An essential concept which defines polymer structure, the repeat unit or repeating unit is a part of a polymer chain whose repetition would produce the complete polymer by linking the repeat units together successively along the chain, like the beads of a necklace.A repeat unit is sometimes called...
repeats and four 9-mer repeats. Ten to 20 monomers of the replication protein dnaA
DnaA
dnaA is a replication initiation factor which promotes the unwinding or denaturation of DNA at oriC , during DNA replication in prokaryotes....
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
DnaC
dnaC is a bacterial gene that codes for protein DnaC. DnaC, also known as the helicase loader, is a regulator of DnaB. DnaC forms a complex with DnaB, thus enabling DnaB to perform its functions in bacterial DNA replication. This interaction of DnaC with DnaB requires the hydrolysis of ATP....
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.
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 sequenceAutonomously replicating sequence
An autonomously replicating sequence contains the origin of replication in the yeast genome. It contains four regions , named in order of their effect on plasmid stability; when these regions are mutated, replication does not initiate....
s or ARS elements. Each budding yeast origin consists of a short (~11 bp
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
) 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-replication complex
A pre-replication complex is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will carry the...
(pre-RC):
- First, the origin DNA is bound by the Origin Recognition ComplexOrigin Recognition ComplexORC or Origin Recognition Complex is a multi-subunit DNA binding complex that binds in all eukaryotes in an ATP-dependent manner to origins of replication....
(ORC) which, with help from two further protein factors (Cdc6Cdc6Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...
and Cdt1), load the Mini Chromosome MaintenanceMini Chromosome MaintenanceMini Chromosome Maintenance complex, or Minichromosome Maintenance protein complex or mini-chromosome maintenance 2-7 helicase complex has a role in both the initiation and the elongation phases of eukaryotic DNA replication, specifically the formation and elongation of the replication fork...
(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
Geminin
Geminin, DNA replication inhibitor, also known as GMNN, is a protein in humans encoded by the GMNN gene.Geminin is a nuclear protein that is present in most eukaryotics and highly conserved across species...
, 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
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
.