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The initiator proteins are the proteins that recognize a specific DNA sequence within the origin of replication. The origin of replication is the site where the helicase attaches to the template strand and starts to unwind the DNA into two strands.
DnaA is a protein that activates initiation of DNA replication in bacteria. [1] Based on the Replicon Model, a positively active initiator molecule contacts with a particular spot on a circular chromosome called the replicator to start DNA replication. [2] It is a replication initiation factor which promotes the unwinding of DNA at oriC. [1]
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.
[11] [10] In E. coli the primary initiator protein is Dna A; in yeast, this is the origin recognition complex. [27] Sequences used by initiator proteins tend to be "AT-rich" (rich in adenine and thymine bases), because A-T base pairs have two hydrogen bonds (rather than the three formed in a C-G pair) and thus are easier to strand-separate. [28]
The replication initiator protein (Rep) plays a key role in initiation of replication in plasmids. In its monomer form, Rep binds an iteron and promotes replication. The protein itself is known to contain two independent N-terminal and C-terminal globular domains that subsequently bind to two domains of the iteron.
The major enzymatic functions carried out at the replication fork are well conserved from prokaryotes to eukaryotes, but the replication machinery in eukaryotic DNA replication is a much larger complex, coordinating many proteins at the site of replication, forming the replisome.
DnaA protein plays a crucial role in the initiation of chromosomal DNA replication. [3] Bound to ATP, and with the assistance of bacterial histone-like proteins [HU] DnaA then unwinds an AT-rich region near the left boundary of oriC, which carries three 13-mer motifs, [4] and opens up the double-stranded DNA for entrance of other replication ...
The ORC4 protein is known to bind the AT-rich portion of the origin of replication in S. pombe using AT hook motifs. The mechanism of origin recognition in higher eukaryotes is not well understood but it is thought that the ORC1-6 proteins depend on unusual DNA topology for binding.