Introduction to The Replicon: Initiation of Replication

Whether a cell has only one chromosome (as in most prokaryotes) or has many chromosomes (as in eukaryotes), the entire genome must be replicated precisely, once for every cell division. How is the act of replication linked to the cell cycle?
Two general principles are used to compare the state of replication with the condition of the cell cycle:
- Initiation of DNA replication commits the cell (prokaryotic or eukaryotic) to a further division. From this standpoint, the number of descendants that a cell generates is determined by a series of decisions about whether to initiate DNA replication. Replication is controlled at the stage of initiation. When replication has begun, it continues until the entire genome has been duplicated.
- If replication proceeds, the consequent division cannot be permitted to occur until the replication event has been completed. Indeed, the completion of replication might provide a trigger for cell division. The duplicate genomes are then segregated, one to each daughter cell. The unit of segregation is the chromosome.
The unit of DNA in which an individual act of replication occurs is called the replicon. Each replicon “fires” once, and only once, in each cell cycle. The replicon is defined by its possession of the control elements needed for replication. It has an origin at which replication is initiated. It can also have a terminus at which replication stops. Any sequence attached to an origin—or, more precisely, not separated from an origin by a terminus—is replicated as part of that replicon. The origin is a cis-acting site, able to affect only that molecule of DNA on which it resides.
(The original formulation of the replicon [in bacteria] viewed it as a unit possessing both the origin and the gene coding for the regulator protein. Now, however, “replicon” is usually applied to eukaryotic chromosomes to describe a unit of replication that contains an origin; trans-acting regulator protein[s] might be encoded elsewhere.)
Bacteria and archaea can contain additional genetic information in the form of plasmids. A plasmid is an autonomous circular DNA that constitutes a separate replicon. Each invading phage or virus DNA also constitutes a replicon, and thus is able to initiate many times during an infectious cycle. Perhaps a better way to view the prokaryotic replicon, therefore, is to reverse the definition: Any DNA molecule that contains an origin can be replicated autonomously in the cell.
A major difference in the organization of bacterial, archaeal, and eukaryotic genomes is seen in their replication. A genome in a bacterial cell has a single replication origin and thus constitutes a single replicon; therefore, the units of replication and segregation coincide. Initiation at a single origin sponsors replication of the entire genome, once for every cell division. Each haploid bacterium typically has a single chromosome, so this type of replication control is called single copy. The other prokaryotic domain of life, the archaea, is more complex. Whereas some archaeal species have chromosomes with a bacterial-like situation of a single replication origin, other species initiate replication from multiple sites on a single chromosome. For example, the single circular chromosomes of Sulfolobus species have three origins and thus are composed of three replicons. This complexity is further heightened in eukaryotes. Each eukaryotic chromosome (usually a very long linear molecule of DNA) contains a large number of replicons spaced unevenly throughout the chromosomes. The presence of multiple origins per chromosome adds another dimension to the problem of control: All of the replicons on a chromosome must be fired during one cell cycle. They are not necessarily, however, active simultaneously. Each replicon must be activated over a fairly protracted period, and each must be activated no more than once in each cell cycle. Multiple mechanisms exist to prevent premature reinitiation of replication.
Some signal must distinguish replicated from nonreplicated replicons to ensure that replicons do not fire a second time. Many replicons are activated independently, so another signal must exist to indicate when the entire process of replicating all replicons has been completed.
In contrast with nuclear chromosomes, which have a single-copy type of control, the DNA of mitochondria and chloroplasts might be regulated more like plasmids that exist in multiple copies per bacterium. There are multiple copies of each organelle DNA per cell, and the control of organelle DNA replication must be related to the cell cycle (see the chapter titled Extrachromosomal Replicons).Introduction
Whether a cell has only one chromosome (as in most prokaryotes) or has many chromosomes (as in eukaryotes), the entire genome must be replicated precisely, once for every cell division. How is the act of replication linked to the cell cycle? Two general principles are used to compare the state of replication with the condition of the cell cycle:
Initiation of DNA replication commits the cell (prokaryotic or
eukaryotic) to a further division. From this standpoint, the
number of descendants that a cell generates is determined by a
series of decisions about whether to initiate DNA replication.
Replication is controlled at the stage of initiation. When replication has begun, it continues until the entire genome has been duplicated.
If replication proceeds, the consequent division cannot be permitted to occur until the replication event has been completed. Indeed, the completion of replication might provide a trigger for cell division. The duplicate genomes are then segregated, one to each daughter cell. The unit of segregationis the chromosome. 
The unit of DNA in which an individual act of replication occurs is called the replicon. Each replicon “fires” once, and only once, in each cell cycle. The replicon is defined by its possession of the control elements needed for replication. It has an origin at which replication is initiated. It can also have a terminus at which replication stops. Any sequence attached to an origin—or, more precisely, not separated from an origin by a terminus—is replicated as part of that replicon. The origin is a cis-acting site, able to affect only that molecule of DNA on which it resides.
(The original formulation of the replicon [in bacteria] viewed it as a unit possessing both the origin and the gene coding for the regulator protein. Now, however, “replicon” is usually applied to eukaryotic chromosomes to describe a unit of replication that contains an origin; trans-acting regulator protein[s] might be encoded elsewhere.)
Bacteria and archaea can contain additional genetic information in the form of plasmids. A plasmid is an autonomous circular DNA that constitutes a separate replicon. Each invading phage or virus DNA also constitutes a replicon, and thus is able to initiate many times during an infectious cycle. Perhaps a better way to view the prokaryotic replicon, therefore, is to reverse the definition: Any DNA molecule that contains an origin can be replicated autonomously in the cell.
A major difference in the organization of bacterial, archaeal, and eukaryotic genomes is seen in their replication. A genome in a bacterial cell has a single replication origin and thus constitutes a single replicon; therefore, the units of replication and segregation coincide. Initiation at a single origin sponsors replication of the entire genome, once for every cell division. Each haploid bacterium typically has a single chromosome, so this type of replication control is called single copy. The other prokaryotic domain of life, the archaea, is more complex. Whereas some archaeal species have chromosomes with a bacterial-like situation of a single replication origin, other species initiate replication from multiple sites on a single chromosome. For example, the single circular chromosomes of Sulfolobus species have three origins and thus are composed of three replicons. This complexity is further heightened in eukaryotes. Each eukaryotic chromosome (usually a very long linear molecule of DNA) contains a large number of replicons spaced unevenly throughout the chromosomes. The presence of multiple origins per chromosome adds another dimension to the problem of control: All of the replicons on a chromosome must be fired during one cell cycle. They are not necessarily, however, active simultaneously. Each replicon must be activated over a fairly protracted period, and each must beactivated no more than once in each c ell cycle. Multiple mechanisms exist to prevent premature reinitiation of replication.
Some signal must distinguish replicated from nonreplicated replicons to ensure that replicons do not fire a second time. Many replicons are activated independently, so another signal must exist to indicate when the entire process of replicating all replicons has been completed.
In contrast with nuclear chromosomes, which have a single-copy type of control, the DNA of mitochondria and chloroplasts might be regulated more like plasmids that exist in multiple copies per bacterium. There are multiple copies of each organelle DNA per cell, and the control of organelle DNA replication must be related to the cell cycle .