Origin of replication

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The origin of replication ( ORI ) or origin for short , also Origo , is the place on a DNA molecule where the replication of the DNA begins.

The origin of replication in bacteria

The origin of replication in bacteria is called ori and there is usually one origin of replication per bacterial chromosome . The best-described oriC is that of the model organism Escherichia coli . This comprises approx. 245 base pairs and is rich in the bases adenine and thymine . The oriC contains some repetitive sequences which, as a consensus sequence, have a base sequence of nine base pairs. This area is called the DnaA box because it is bound by the DnaA protein. The binding of the protein induces a curvature in the DNA, which denatures the DNA in the area of ​​the DnaA box. This is also made possible by the high number of adenine and thymine already mentioned. These bases form two hydrogen bonds with one another , in contrast to guanine and cytosine, which form three hydrogen bonds with one another (see also Watson-Crick base pairing ). DnaA destabilizes the double-stranded structure of the DNA by tension, which causes the two strands to unwind. After being untwisted by DnaA, DnaB can bind. For this binding, the protein DnaC is also required, which causes the binding of DnaB to the melted piece of DNA. The protein DnaB is a helicase that enlarges the melted area in both directions. DnaC has an AAA- ATPase domain, which has different binding properties when ADP and ATP bind. It is postulated that the binding of ATP causes the DNA to bind more strongly. It is also observed that DnaC-ATP inhibits the helicase activity of DnaB. DnaC-ATP probably has the task of binding DnaB to the DNA, whereupon the ATPase function hydrolyzes the bound ATP to ADP and then the helicase can do its work. In addition, the origin of replication appears to be related to the bacterial cell cycle. It must be ensured that the chromosome is only duplicated once per cell cycle. This seems to be controlled by the degree of methylation of the oriC.

The origin of replication in eukaryotes using the example of baker's yeast

In eukaryotes , the identification and description of the origins is more difficult. The number of origins of replication is not limited to a single one per chromosome, but can range from several hundred to 1000 origins. In the baker's yeast Saccharomyces cerevisiae , the origins represent non-coding regions of 100 to 200 base pairs, which are referred to as ARS (autonomously replicating sequences). Analogous to the protein DnaA, yeasts have the origin of replication complex (Orc), which can be attached to the ARS sequences. The MCM ( minichromosomal maintenance ) complex probably represents the helicase and can be compared with DnaB. There is also a “loading complex” (comparable to DnaC) with baker's yeast which binds MCM. However, the interactions between the individual components seem more diverse. For example, interactions with ORC may also be necessary for the binding of the helicase. In addition, here again ATPase functions of the individual components seem to influence the binding properties. Due to the variety of interactions and initiation complex components, it is helpful to compare the process in S. Cerevisiae with E. Coli . However, these are processes that have been developed in an analog manner, differ from one another in detail and work in different molecular ways.

Replication in higher eukaryotes

In higher eukaryotes, such as B. insects or vertebrates, research is often still at the level of the identification of the individual components. In addition, it is more difficult to recognize the origins, since no consensus sequences or special non-coding areas have been found so far, and no general statements about the "appearance" can be made. Since there are already signs of epigenetic mechanisms in baker's yeast , one can assume that the process is even more complicated in more highly developed organisms.

Replication in archaea

Research is still in its infancy here , but archaea could be a starting point to better understand the process in eukaryotes. These have relatively simply structured chromosomes, which are similar to those of bacteria. However, the molecular mechanisms of information processing from DNA are more similar to those of eukaryotes. In some cases homologies to yeast proteins have already been found, which gives rise to the hope that the archaea can be used as simple model organisms for eukaryotes.

See also

Individual evidence

  1. ↑ Origins of DNA replication in the three domains of life, NP Robinson & S. Bell, FEBS Journal 272 (2005), 3757-3766
  2. ^ A b Nelson, Cox: Lehninger Biochemie 3rd edition, Springer-Verlag, Berlin 2001. ISBN 3-540-41813-X

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