Termination Eukaryotic chromosomes have multiple origins of replication, which initiate replication almost simultaneously. Key Points During initiation, proteins bind to the origin of replication while helicase unwinds the DNA helix and two replication forks are formed at the origin of replication. During elongation, a primer sequence is added with complementary RNA nucleotides, which are then replaced by DNA nucleotides. During elongation the leading strand is made continuously, while the lagging strand is made in pieces called Okazaki fragments.
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Mol Cell 63 : — Curr Biol 22 : — Four deoxyribonucleotide triphosphates dNTP's are required for DNA synthesis note the only difference between deoxyribonucleotides and ribonucleotides is the absence of an OH group at position 2' on the ribose ring. The high energy phosphate bond between the a and b phosphates is cleaved and the deoxynucleotide monophosphate is incorporated into the new DNA strand.
The nucleotide that is to be incorporated into the growing DNA chain is selected by base pairing with the template strand of the DNA. An enzyme, DNA polymerase, is required for the covalent joining of the incoming nucleotide to the primer.
To actually initiate and sustain DNA replication requires many other proteins and enzymes which assemble into a large complex called a replisome.
It is thought that the DNA is spooled through the replisome and replicated as it passes through. The major catalytic step of DNA synthesis is shown below. Notice that DNA synthesis always occurs in a 5' to 3' direction and that the incoming nucleotide first base pairs with the template and is then linked to the nucleotide on the primer.
Since all known DNA polymerases can synthesize only in a 5' to 3' direction a problem arises in trying to replicate the two strands of DNA at the fork. Notice that the top strand must be discontinuously replicated in short stretches thus the replication of both parental strands is a semidiscontinuous process.
The strand that is continuously synthesized is called the leading strand while the strand that is discontinuously synthesized is called the lagging strand. A primase synthesizes the ribonucleotide primer ranging from 4 to 12 nucleotides in length. DNA polymerase then incorporates a dNMP onto the 3' end of the primer initiating leading strand synthesis.
Only one primer is required for the initiation and propagation of leading strand synthesis. As the leading strand is synthesized along the lower parental strand the top parental strand becomes exposed. The strand is then recognized by a primase which synthesizes a short RNA primer.
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