Voltage-gated Na+ channels are highly concentrated in the nodes of Ranvier and the initial segment in myelinated neurons. 

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#Unit 3. Fundamental Processes

Before replication, the palindromic target GATC site is methylated by dam methylase on the N6 of A of each strand.

Replication generates hemimethylated DNA, in which one strand is methylated and one strand is unmethylated.

Thus, the replication event converts Dam target sites from fully methylated to hemimethylated condition.

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#Unit 3. Fundamental Processes

Dam (Dam-) mutants accumulates hemimethylated products after replication.

If the plasmid is methylated, it undergoes a single round of replication, and then the hemimethylated products accumulate.

Suggesting that a hemimethylated origin cannot be used to initiate a replication cycle.

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#Unit 3. Fundamental Processes

Only fully methylated origins can initiate replication;

hemimethylated daughter origins cannot be used again until they have been restored to the fully methylated state.

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#Unit 3. Fundamental Processes

The GATC sites AT THE ORIGIN remain hemimethylated for 13 minutes after replication called as refractory period of replication cycle or delay time.

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#Unit 3. Fundamental Processes

At typical GATC sites elsewhere in the genome, remethylation begins immediately (1.5 minutes) following replication.

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#Unit 3. Fundamental Processes

One other region behaves like oriC:

The promoter of the dnaA gene also shows a delay before remethylation begins.

While it is hemimethylated, the dnaA promoter is repressed, which causes a reduction in the level of DnaA protein.

So Initiation of Replication (E.coli) takes place when GATC at origin is full methylated as well as promoter of DnaA gene.