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My name is Louis Aragón
and I'm a group leader and
professor in Genetics at
Imperial College
London in the UK.
Today I will be talking to you
about cellular
mechanisms that ensure
the completion of
replication during
S phase of the cell cycle.
By promoting replication
forks stability,
and processivity when
the DNA template
presents obstacle to the
replication process.
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To begin with, we will look at
the basic anatomy of
replication forks.
For the purpose of
this presentation,
we will focus on a
characteristic systems.
Now, the replication
fork is a structure
which forms when DNA
is being replicated.
It is created with the action of
the replicative helicases
or the MCM complex,
which uncoils the
parental strands so
that each strand
of DNA is exposed.
Replicative helicases are
loaded at origins and
carry out the job of
leading the forks
throughout the genome,
the replicating forecast has two
strands, the leading strand,
which is synthesized
in the five prime to
three prime direction
in a continuous manner.
The lagging strand,
which is opposite to
the Leading and runs in the
three prime to
five-prime direction.
Because polymerases can only
synthesized in the five
to three direction.
The lagging strand
is synthesized in
short segments known
as Okazaki fragments.
Along the lagging
strand template
primates bills RNA fragments
in short bursts.
DNA polymerases are
then able to use a
three-prime ends on the RNA
primers to synthesize DNA,
the five to three
prime direction.
The RNA fragments
are then removed by
DNA polymerase and
finally the segments of
the newly synthesized strand
are joined together by
ligase completing their
synthesis of the lagging strand.
Each strand is synthesized
by dedicated polymerases.
The leading strand polymerases
polymerase delta and epsilon,
while the lagging strand
polymerases is polymerase Alpha.
As the fork unfolds
single stranded regions
are expose and these
have the tendency
to fall back upon
themselves and formed a
secondary structures.
Such structures can interfere
with the movement
of DNA polymerases.
Therefore, to prevent
this from happening,
single-stranded binding
proteins named RPA,
binds to the single-stranded DNA
until the second
strand is synthesized.
A clump protein named PCNA
or proliferating cell
nuclear antigen from
sliding come around DNA,
helping their DNA polymerase
maintain contact with
the template and thereby
assisting with processivity.
Once the polymerase
reaches the end of
the template or the texts
double-stranded DNA,
the sliding clamp undergoes
a conformational change,
will release the DNA polymerase.
A clamp loading complex called
replication factor C is used
to initially load the clamp,
recognizing the junction between
the template and
the RNA primers.
Following passage
and replication,
the cohesion complex is loaded,
therefore holding the
sister chromatids together.
Now the ability of a cell
to faithfully replicate
