I talked earlier about the value of proofreading
and help in maintaining the integrity of the DNA.
The cell has other mechanisms of
helping to maintain that integrity;
because, the integrity is pretty critical because that
DNA is gonna be the information for the next generation.
So in addition to the proofreading that
I have described in the DNA polymerase
there are some other repair
systems that help the cell
try to avoid problems and I will
say few words about these.
So the integrity is critical, as I said, and
proofread only provides some of the protection
The other systems provide protection against
things like for example chemical damage
or errors that didn't get copy by the proofreading
or some other things that happened to the DNA.
One of these happens as result of
staying out in the sun for too long.
UV damage to the DNA can cause something called thymine
dimers to form. Thymine dimers are pretty serious.
So there are three primary systems for repair of DNA
that I wanna mention. They called base excision repair.
They are called nucleotide excision
repair and the third is mismatch repair.
Now they all have different proteins and
different mechanisms of functioning
functions but they all have
some common features as well.
In each case a problem is recognized by the
cell. I have labelled it here as a damaged base.
That damage base might be a thymine dimer
which are two thymines that have been joined
together, because, of the exposure to the UV light.
That damaged base might be some DNA
adduct that got struck onto it.
But that damaged base could even
be an error in the base pairing
that happened that didn't get caught by the proofreading.
It doesn't matter really how it got there.
But the proteins of each of these systems
will recognize and bind to
that base and depending upon
which type of error it is determines which
system actually kicks in to do it.
In the process of fixing this error
we can see what happens is
that the strand that has the
damaged base, as you can see on top,
is cleaved to make a little gap that you
see there. You see the strand lifting up
and now you see a new 3 prime hydroxyl
and you see a 5 prime region as well.
These repair systems will take
that strand and excise it.
So we have seen how exonucleases, for
example, can excise or cut away
the phosphodiester bonds and
we see that process happening below
that gap. On the left, we see the
peeling away in the replication first
in other cases we can see the removal
on the right and then the replication later and
again for our purposes it's not really significant.
The bottom line is that the
DNA polymerase comes back in
and fills in that gap using the base
pairing rules that it had before.
DNA ligase joins the pieces together and the
DNA hopefully has been repaired in that process.
So the damaged base is a critical
part of that overall process.
It has to be recognized; because, if
it's not recognized then, then of course,
other problems will arise. The problem has to be
taken care of by the proteins that I have mentioned.
And finally resolved by the exonucleases
removing the damage, the DNA polymerase
filling in the gap and DNA ligase
taking care of the final product.
We can see in this figure here one of these systems
in place. This is a nucleotide excision repair system
and you see one of the proteins that's
involved in this process in green.
It is bound to a DNA that has had a problem
and the problem is a base
that's in there, shown in yellow.
The strand has peeled away
from the duplex, as you can see,
and that peeling away has happened
by this protein of the system.
It is getting ready to remove the
base which is shown in yellow.
And then that overall system that
I talked about will kick in
to cut the strand, remove the piece, DNA polymerase
filled it in and DNA ligase repair the damage.
So single strand repair systems which
are what I am talking about here
are all very important for us. Problems with these
systems have enormous implications for human health.
Nucleotide excision repair problems are
associated with xeroderma pigmentosa, a very
important problem relating to sun
sensitivity and cockayne syndrome.
Deficiencies of overloading the base repair systems
may be associated with cancer susceptibility.
So I have heard numerous times about the dangers
of being out and getting too much exposure to the sun
and that probably happens because the
DNA damage that I described earlier.
Finally, mismatch repair deficiency
is a factor in hereditary
nonpolyposis colorectal cancer,
the most common type of
colorectal cancer that occurs.
Well, I have gone through now the
processes of DNA replication in both
prokaryotic and eukaryotic systems and I have
tried to give some feel for the repair system
that help maintain the integrity of the DNA.
I hope what you have taken
away from this presentation
is the importance of replicating DNA properly
and taking care of it and that the cell
is heavily invested in these processes.