The origin of replication (also called the replication origin) is a particular sequence in a genome at which replication is initiated. Propagation of the genetic material between generations requires timely and accurate duplication of DNA by semiconservative replication prior to cell division to ensure each daughter cell receives the full complement of chromosomes. This can either involve the replication of DNA in living organisms such as prokaryotes and eukaryotes, or that of DNA or RNA in viruses, such as double-stranded RNA viruses. Synthesis of daughter strands starts at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, organisms have evolved surprisingly divergent strategies that control replication onset. Although the specific replication origin organization structure and recognition varies from species to species, some common characteristics are shared.
Features A key prerequisite for DNA replication is that it must occur with extremely high fidelity and efficiency exactly once per cell cycle to prevent the accumulation of genetic alterations with potentially deleterious consequences for cell survival and organismal viability. Incomplete, erroneous, or untimely DNA replication events can give rise to mutations, chromosomal polyploidy or aneuploidy, and gene copy number variations, each of which in turn can lead to diseases, including cancer. To ensure complete and accurate duplication of the entire genome and the correct flow of genetic information to progeny cells, all DNA replication events are not only tightly regulated with cell cycle cues but are also coordinated with other cellular events such as transcription and DNA repair. Additionally, origin sequences commonly have high AT-content across all kingdoms, since repeats of adenine and thymine are easier to separate because their base stacking interactions are not as strong as those of guanine and cytosine. DNA replication is divided into different stages. During initiation, the replication machineries – termed replisomes – are assembled on DNA in a bidirectional fashion. These assembly loci constitute the start sites of DNA replication or replication origins. In the elongation phase, replisomes travel in opposite directions with the replication forks, unwinding the DNA helix and synthesizing complementary daughter DNA strands using both parental strands as templates. Once replication is complete, specific termination events lead to the disassembly of replisomes. As long as the entire genome is duplicated before cell division, one might assume that the location of replication start sites does not matter; yet, it has been shown that many organisms use preferred genomic regions as origins. The necessity to regulate origin location likely arises from the need to coordinate DNA replication with other processes that act on the shared chromatin template to avoid DNA strand breaks and DNA damage.
… excerpt ends here. Continue reading the full article.
![Origin of replication: Origin organization and recognition in bacteria. A) Schematic of the architecture of E. coli origin oriC, Thermotoga maritima oriC, and the bipartite origin in Helicobacter pylori. The DUE is flanked on one side by several high- and weak-affinity DnaA-boxes as indicated for E. coli oriC. B) Domain organization of the E. coli initiator DnaA. Magenta circle indicates the single-strand DNA binding site. C) Models for origin recognition and melting by DnaA. In the two-state model (left panel), the DnaA protomers transition from a dsDNA binding mode (mediated by the HTH-domains recognizing DnaA-boxes) to an ssDNA binding mode (mediated by the AAA+ domains). In the loop-back model, the DNA is sharply bent backwards onto the DnaA filament (facilitated by the regulatory protein IHF)[38] so that a single protomer binds both duplex and single-stranded regions. In either instance, the DnaA filament melts the DNA duplex and stabilizes the initiation bubble prior to loading of the replicative helicase (DnaB in E. coli). HTH – helix-turn-helix domain, DUE – DNA unwinding element, IHF – integration host factor.](https://upload.wikimedia.org/wikipedia/commons/thumb/6/61/Origins_of_DNA_replication_Figure_2.jpg/1280px-Origins_of_DNA_replication_Figure_2.jpg?utm_source=en.wikipedia.org&utm_campaign=parser&utm_content=thumbnail)
![Origin of replication: Origin organization and recognition in eukaryotes. Specific DNA elements and epigenetic features involved in ORC recruitment and origin function are summarized for S. cerevisiae, S. pombe, and metazoan origins. A schematic of the ORC architecture is also shown, highlighting the arrangement of the AAA+ and winged-helix domains into a pentameric ring that encircles origin DNA. Ancillary domains of several ORC subunits involved in targeting ORC to origins are included. Other regions in ORC subunits may also be involved in initiator recruitment, either by directly or indirectly associating with partner proteins. A few examples are listed. Note that the BAH domain in S. cerevisiae Orc1 binds nucleosomes[102] but does not recognize H4K20me2.[103]BAH – bromo-adjacent homology domain, WH – winged-helix domain, TFIIB – transcription factor II B-like domain in Orc6, G4 – G quadruplex, OGRE – origin G-rich repeated element. ORC gene names are indicated by a single number; e.g. 3 refers to ORC3.](https://upload.wikimedia.org/wikipedia/commons/thumb/1/1c/Origins_of_DNA_replication_Figure_4.jpg/1280px-Origins_of_DNA_replication_Figure_4.jpg?utm_source=en.wikipedia.org&utm_campaign=parser&utm_content=thumbnail)
