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Site selection for replication origins is carried out by the Origin Recognition Complex (ORC), a six subunit complex (Orc1-6). [ 12 ] [ 13 ] During the G1 phase of the cell cycle, Cdc6 is recruited by ORC to form a launching pad for the loading of two head-to-head Mcm2-7 hexamers, also known as the pre-replication complex (pre-RC). [ 14 ]
The ORC is essential for the loading of MCM complexes onto DNA. This process is dependent on the ORC, Noc3, Cdc6, and Cdt1 – involving several ATP controlled recruiting events. First, the ORC, Noc3p and Cdc6 form a complex on origin DNA (marked by ARS type regions). New ORC/Noc3/Cdc6 complexes then recruit Cdt1/Mcm2-7 molecules to the site.
This timing and other regulatory mechanisms ensure that DNA replication will only occur once per cell cycle. Assembly of the pre-RC relies on prior origin recognition, either by DnaA in prokaryotes or by ORC in archaea and eukaryotes. The pre-RC of prokaryotes is complete when DnaA occupies all possible binding sites within the oriC.
More than five decades ago, Jacob, Brenner, and Cuzin proposed the replicon hypothesis to explain the regulation of chromosomal DNA synthesis in E. coli. [18] The model postulates that a diffusible, trans-acting factor, a so-called initiator, interacts with a cis-acting DNA element, the replicator, to promote replication onset at a nearby origin.
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The Michoud Assembly Facility (MAF) is an 832-acre (337-hectare) industrial complex for the manufacture and structural assembly of aerospace vehicles and components. It is owned by NASA and located in New Orleans East , a section of New Orleans, Louisiana , in the United States.