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DNA Repair

by Kevin Ahern, PhD
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    00:00 I talked earlier about the value of proofreading and help in maintaining the integrity of the DNA.

    00:06 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.

    00:15 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.

    00:26 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.

    00:44 One of these happens as result of staying out in the sun for too long.

    00:48 UV damage to the DNA can cause something called thymine dimers to form. Thymine dimers are pretty serious.

    00:57 So there are three primary systems for repair of DNA that I wanna mention. They called base excision repair.

    01:03 They are called nucleotide excision repair and the third is mismatch repair.

    01:08 Now they all have different proteins and different mechanisms of functioning functions but they all have some common features as well.

    01:15 In each case a problem is recognized by the cell. I have labelled it here as a damaged base.

    01:22 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.

    01:29 That damaged base might be some DNA adduct that got struck onto it.

    01:34 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.

    01:44 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.

    01:57 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.

    02:17 These repair systems will take that strand and excise it.

    02:21 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.

    02:44 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.

    02:52 DNA ligase joins the pieces together and the DNA hopefully has been repaired in that process.

    03:00 So the damaged base is a critical part of that overall process.

    03:04 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.

    03:13 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.

    03:22 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.

    03:33 It is bound to a DNA that has had a problem and the problem is a base that's in there, shown in yellow.

    03:40 The strand has peeled away from the duplex, as you can see, and that peeling away has happened by this protein of the system.

    03:48 It is getting ready to remove the base which is shown in yellow.

    03:53 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.

    04:05 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.

    04:16 Nucleotide excision repair problems are associated with xeroderma pigmentosa, a very important problem relating to sun sensitivity and cockayne syndrome.

    04:29 Deficiencies of overloading the base repair systems may be associated with cancer susceptibility.

    04:34 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.

    04:45 Finally, mismatch repair deficiency is a factor in hereditary nonpolyposis colorectal cancer, the most common type of colorectal cancer that occurs.

    04:56 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.

    05:08 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.


    About the Lecture

    The lecture DNA Repair by Kevin Ahern, PhD is from the course DNA Replication and Repair.


    Included Quiz Questions

    1. It requires unusual DNA polymerases
    2. Deficiencies in it are linked to human cancer
    3. It can cut out damaged bases
    4. It can fix thymine dimers
    1. Visible part of electromagnetic spectrum — cause damage during DNA replication
    2. UV damage — thymine dimer formation
    3. Nucleotide excision repair deficiency — xeroderma pigmentosum
    4. Mismatch repair deficiency — nonpolyposis colorectal cancer
    5. Thymine dimer repair — photoreactivation repair

    Author of lecture DNA Repair

     Kevin Ahern, PhD

    Kevin Ahern, PhD


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    Well-organized content
    By Glen K. on 15. March 2018 for DNA Repair

    Care for details and passion/curiosity for knowledge are seen in this lecture. I gained a lot from it.

     
    Really liked It
    By Orlando U. on 27. February 2018 for DNA Repair

    Very profesional, why is it said that bacterial chromosome has a single origin of replication and eukaryotic multiple origins

     
    Thank you
    By Abhay K. on 12. February 2018 for DNA Repair

    Thank you so much Sir for brief description of all topics.

     
    Well explained, using simple terms
    By Siddhant G. on 07. December 2017 for DNA Repair

    This lecture was very educational, and well organised, moving from the basics to the complicated topics, explaining every topic step by step.

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