Replication models

1. K. Narayanapura, Kothanur (PO), Bengaluru 560077
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MODELS OF REPLICATION
Dr. Manikandan Kathirvel
Assistant Professor,
Department of Life Sciences,
Kristu Jayanti College (Autonomous),
Bengaluru

2. Model of replication
■ Each chain of double helix acts as template and is
evolved in replication of DNA.
■ Watson and Crick proposed that the hydrogen
bonds between the base pairs of two strands are
broken and separated from each other.
■ Each purine and pyrimidine base of the strands
forms hydrogen bonds with complementary free
nucleotides to be involved in polymerization in the
cell.
■ The free nucleotides form phosphodiester bonds
with deoxyribose residue resulting in formation of a
new polynucleotide molecule .
■ This model of Watson and Crick for DNA replication
was later on verified experimentally.
One of the most important properties of DNA functioning
as the genetic material is that it can make exact copies of
itself (autocatalytic function) forming the basis for
transmission of hereditary characters it controls.
This process is called replication.

3. MODELS 0F REPLICATION
■ 1.ASYMMETRIC REPLICATION
■ 2.ROLLING CIRCLE MODEL
■ 3.D-LOOP MODEL
CONCATEMER FORMATION

4. The leading strand and lagging strand that are unwound by the DNA helicase at the replication fork
run in opposite directions, but the new DNA sequences are synthesized in only one direction, i.e., 5’
to 3’ direction, because the enzymes involved in DNA replication can only work in the 5’ to 3’
direction.
Therefore, these two template strands are replicated in different ways, resulting in the asymmetry of
DNA replication.
During DNA replication, the leading strand can be continuously replicated by the polymerase since its
template strand is in the 3’ to 5’ direction.
However, the replication of the lagging stand is not so straightforward. It cannot be created in a
continuous manner due to the 5’ to 3’ directionality of its template strand. Polymerases need to work
backwards from the replication fork, creating periodic breaks in the process of replicating the lagging
strand. DNA fragments, rather than continuous DNA sequence as in the leading strand, are
generated in the lagging strand. These fragments, known as Okazaki fragments, are then connected
into a single, continuous strand by the DNA ligase. In this way, the entire replication process is
completed and it is considered asymmetric because of the difference in replicating these two strands.
I). ASYMMETRIC REPLICATION

5. I). ASYMMETRIC REPLICATION
■ The sequences of the two strands of a DNA molecule run in
opposite directions, but during replication the new DNA
molecules are synthesized in only one direction, because
the enzymes involved in DNA replication can only work in
the 5’ to 3’ direction.
■ Each strand is therefore duplicated differently.
■ The leading strand is used as a template by a polymerase
enzyme (Pol ε), which makes a new molecule in a
continuous manner.
■ By contrast, duplication of the lagging strand is discontinuous
and requires another polymerase (Pol δ), which synthesizes
short DNA pieces known as Okazaki fragments.
■ These okazaki fragments are then joined together with the
help of other enzymes to form a continuous molecule.
■ During the process, nucleosomes-protein complexes around
which DNA is coiled-disassemble from parental DNA to then
reassemble, along with additional nucleosome proteins as
needed, allowing both DNA duplication and chromatin
reorganization.

6. II). D-LOOPED MODEL
This mode of replication occurs in mammalian mitochondria and
Chloroplast
 The mitochondrial chromosome in circular. One strand of the
chromosome is denoted as H strand, while its complementary
strand is named L strand.
■ Replication begins at a specific origin, but only one strand, the
H strand, is replicated; the other strand (the L strand) of the
chromosome is displaced forming a loop, called displacement
loop or D loop.
■ When replication of (the H strand) has progressed up to about
2/3 of the chromosome, the replication of the displaced single
strand (L strand) begins.
■ This replication begins at a different origin and replication
proceeds in the opposite direction.
■ Thus both the strands of DNA are replicated in a continuous
manner, their replications begin at different origins, and
replication of one strand (H strand) begins much earlier than that
of the other (L strand).
■ In this case, replication is not only unidirectional, but the
replication of only one of the two strands takes place at each of
the replication forks

7. III). ROLLING CIRCLE MODEL
■ Rolling circle replication is a process which a circular
DNA or RNA molecule is replicated in one direction.
■ This particular process occurs in plasmid and virus’s
genome.
■ The process of DNA is initiated by initiator protein
which nicks at the site called the double-stranded origin
on one strand of the double-strand.
■ The initiator protein remains on the 5’ phosphate nick
strand, and the 3’ hydroxyl end of the nicked strand is
elongated by DNA polymerase III.
■ The unnicked strand acts as the template strand for
replication and the 5’ phosphate nick strand is displace by
helicase.
■ Eventually, the nick strand is completely displaced by
newly synthesised strand and will remove itself from the
original circular DNA by the same initiator protein nicking
at the terminating sequence on the nicked strand.
■ The nicked strand then form a new single-stranded
circular DNA molecule. RNA polymerase and DNA
polymerase III then use the single strand as a template to
form new double-stranded circular DNA molecule.

8. A concatemer is a long continuous DNA molecule that contains multiple copies of the
same DNA sequence linked in series.
These polymeric molecules are usually copies of an entire genome linked end to end and
separated by cos sites (a protein binding nucleotide sequence that occurs once in each
copy of the genome).
Concatemers are frequently the result of rolling circle replication, and may be seen in the
late stage of bacterial infection by phages.
As an example, if the genes in the phage DNA are arranged ABC, then in a concatemer
the genes would be ABCABCABCABC and so on (assuming synthesis was initiated
between genes C and A). They are further broken by ribozymes.
During active infection, some species of viruses have been shown to replicate their
genetic material via the formation of concatemers. In the case of human herpesvirus-6, its
entire genome is made over and over on a single strand. These long concatemers are
subsequently cleaved between the pac-1 and pac-2 regions by ribozymes, when the
genome is packaged into individual virions.
Concatemer