So it's important to understand what leading
strand replication and lagging strand replication
are and why they occur. Why does
the cell make it hard?
Well the answers to the "Why?"
is rooted in two things.
One we know that the strands
of DNA are anti-parallel.
The top strand is going 5 prime to 3 prime and
the bottom strand is going 3 prime to 5 prime,
okay? The other reason why this is
important is that DNA polymerases
can only work in the 5 prime to 3 prime direction.
Now that's important; because, that means that we
can't, for example, start replicating the top strand
and remember that the top strand here has the 3 prime
end on the left side and the 5 prime end on the right side.
Which means that when replication of it
starts in the anti-parallel fashion
it's going to start 5 prime with a new strand.
Here is the replication of the top strand
and here is the replication of the bottom strand
if it would occur in the same direction.
Well it can't occur in the
same direction; because,
this would mean the polymerase would
have to be working 3 prime to 5 prime.
And I have already given you the rule that
polymerase only works 5 prime to 3 prime.
So this scheme that we see on
this up here cannot happen.
Otherwise we will make either
a DNA that's not anti-parallel
or we would be violating the rule of the DNA polymerase
that it can't go 3 prime to 5 prime. There is a problem.
So instead of doing what I showed on this screen,
the replication of the bottom strand has to
start internally and then move leftwards
and we will see how that happens here.
So we have seen now that the top strand which is
actually the leading strand on this replication system,
the top strand has advanced far along
and it has opened up some regions
on the bottom strand in green.
As the top strand has been
peeled further and further away
more of the bottom strand has been open
and the primase, which made the primer,
and the DNA polymerase have started pointing
things that way. And the further in
the replication fork gets in, the more
of the bottom strand is exposed.
So the more exposure allows for more fragments.
So we can see here is the leading strand in
one piece and here is the lagging strand.
And by the way, as the figure says, the lagging strand
has fragments have a name, they are called Okazaki Fragments,
named for the person who discovered them.
As this replication proceeds we can now see that
the leading strand is still staying in one piece.
Where the lagging strand is having the catch up
in the individual pieces moving leftwards here.
So this ultimately results in the bottom
strand, even though it starts out
in multiple pieces being joined
together into one bigger strand
and that happens because of what we saw earlier.
The removal of the RNA primers and the
joining of the pieces by DNA ligase.
So that ligase plays a really
important role in making that
bottom Okazaki Fragment strand contiguous.
And what happens with that then is we will
ultimately completely replicate both strands
and have the situation that you see on the screen.
Now I showed you in the circuital figure
earlier the removal of primers
and I did that for a purpose even though I
cheated a little bit in making that replication.
I did it to show you an important concept.
The important concept is that as we
go around a circular DNA molecule
it will always come to back where you started
even if it took couple of steps to get there.
That means it's easy to remove the primer and
when you remove the primer it's easy to fill in the
gap and you have two complete strands.
Eukaryotic cells don't have that luxury.
The DNA in eukaryotic chromosomes is in
linear, as you can see on the screen.
Now if you replicate a linear system
and you start with a RNA primer
you can remove them but then you can't replace them;
because, you have nothing else coming
back around to help you with that,
okay? Those sequences that were primers
at the end of a linear eukaryotic DNA
are lost with each round of replication.
That means, therefore, that linear eukaryotic
chromosomes get shorter every time they replicate.
And that means that the DNAs in a person like me
who is probably older than
a person like you, has shorter DNAs;
because, of this phenomena. This has
enormous human health implications.
An important question about the linear chromosomes
in eukaryotic cells is "Why do they not disappear?"
Well to answer that question we have to learn a
little bit about the structure of eukaryotic chromosomes.
So we can see on this diagram a eukaryotic linear
chromosome that has gone through different levels of
replication. The one on the top has had the least number
of replications and the one on the bottom has had the most.
As you can see that blue portion of the chromosome is
getting shorter and shorter with each round of replication.
Now that portion of the chromosome
is a very critical part of it.
That critical part of the
chromosome is known as a telomere.
And the telomere is actually built
to be short, as we shall see.