by Kevin Ahern, PhD

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      12 Advanced DNAReplication&DNARepair.pdf
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    00:00 So what you see on the screen here are some antibody stained chromosomes and their antibodies are designed to bind specifically to the telomeres.

    00:11 And when you see the telomeres, not surprisingly based on what I just told you, they are always at the ends of a DNA.

    00:18 Now telomeres are interesting sequences. They are short pieces of DNA that are replicated over and over and over and over, okay? Now the sequences vary between about 3,000 and 20,000 base pairs at the end of a chromosome.

    00:36 And when they were first discovered, people described them as junk DNA; because, they didn't code for protein and they had this really odd feature that they were just repeats of the same sequence.

    00:48 In humans the sequences are repeats of TTAGGG.

    00:52 And so that was just sort of a mindless sequences and that's why they originally called junk DNA.

    00:57 But it later it become apparent why these sequences were important.

    01:02 If you loose this repeated sequence and this repeated sequence does not code for protein, then shortening the sequence has very little effect until you lose all the repeats.

    01:14 Now some people think that the cellular life span is actually linked to telomere length.

    01:20 The longer the telomeres, the longer the lifespan; because, once you shorten past the point where those repeats are you gonna start losing critical DNA.

    01:30 How do the telomers get there? The telomeres in eukaryotic cells have to be built in each generation.

    01:37 And they are built by germ cells and embryonic cells, as we shall see.

    01:41 Now the building of the telomers requires action of an enzyme known as telomerase.

    01:48 Telomerase works as follows.

    01:50 So telomerase is also a reverse transcriptase and it's a very unusual reverse transcriptase. Now I'd remind you that reverse transcriptase is an enzyme that makes DNA by copying RNA. So, how does it work? The telomerase enzyme, the unusual thing it does, is it carries a template strand with it, that is something to copy.

    02:18 And the telomerase is present primarily in embryonic cells and in cancer cells.

    02:27 Now let's look at how the telomerase functions and then we will have a better idea about how the telomerase themselves get made.

    02:35 You can see on the image here that there is a eukaryotic chromosome the left portion of which is in yellow and then there is a little gap and at that gap you see the blue strand at the bottom and the outline of the telomerase.

    02:49 So the telomerase has brought this blue strand to the end of this linear chromosome.

    02:55 And if it's formed base pairs between the A and the T, the A and the T and the G and the C.

    02:59 So you see those three base pairs at the joint between the blue and the yellow strands above.

    03:05 So the blue again is the RNA template that the telomerase has brought.

    03:12 What the telomerase does after making these base pairs is if you look at the top strand it's pointed in the 5 prime to 3 prime direction. What does it do? It takes that as a primer and it extends it. So it extends the primer and copies the RNA that it is carrying.

    03:30 And then what does it do? It slides down.

    03:34 And so it keeps copying the same sequence, over and over and over and over.

    03:40 In doing that, the repeat of the telomere is made.

    03:44 Now this can happen thousands of time lengthening and lengthening and lengthening and lengthening the eukaryotic chromosome.

    03:51 So after that top strand has been replicated now the bottom strand can also be made. But again remember this is gonna be like the lagging strand that's gonna be made in pieces.

    04:02 So the pieces are going to involve primase and then moving inwards.

    04:06 Now the very last primer at the very far end is not going to be replaced.

    04:12 But the telomere has grown by thousands of bases in the process and enabled that chromosome to be ready for the next generation.

    04:22 So there we have the newly added repeat. There is the primase that has made the RNA primer and now we see on the other strand that is the bottom strand is replicated.

    04:31 And in doing so the eukaryotic chromosome has been replicated.

    About the Lecture

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

    Included Quiz Questions

    1. They are short repeated sequences at the ends of eukaryotic chromosomes
    2. They grow in length with each round of replication
    3. They are created and destroyed by the enzyme known as telomerase
    4. They are made by repeatedly copying a short DNA template
    1. It makes telomeres by repeated copying a short RNA
    2. It is active in almost every cell
    3. It makes cells cancerous when it is inhibited
    4. It uses DNA ligase

    Author of lecture Telomeres

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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