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In this amazing video, at 26:03 we see this imageenter image description here

We now know that the telomerase contains a sequence complementary to the telomere sequence and so is able to do what it is capable of doing in this image.

My questions : What if we make a piece of dna with five GGGGG at the 3' end ? Will the telomerase not work, as the RNA in telomerase has the sequence AACCCC and so won't be able to form complementary strand ? If so, has such a mutation been detected in any organism ie it's telomerase is unable to work just because it has a random insertion(maybe during replication) of one of the nucleotides in the telomere at the 3' end ?

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  • $\begingroup$ Anyone who wishes to understand telomere and telomerase and want to know more about them from the discoverer of telomerase HERself please see the video I mentioned in the link! It's enlightening. $\endgroup$
    – biogirl
    Mar 16, 2014 at 11:25

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This is speculation, as I haven't done or read of the required experiment. However, I imagine that this would not be a problem.

You're right that the RNA template (TERC) would not hybridize with a poly-G sequence, and so the telomerase would not be able to add more telomere repeats. You can imagine that the poly-G sequence is a cap, preventing telomerase activity.

However, without the telomere repeats other proteins are likely to recognize the chromosome end as a DNA break. Exonucleases would likely chew at the end of the chromosome until they got to the actual telomere sequence, which is bound by protective proteins (namely Shelterin). With the poly-G region degraded, the end of the chromosome would now have the true telomere repeats, and telomerase would be able to add even more repeats.

Even if the poly-G region was bound by protective proteins, the telomeres naturally shorten with each replication cycle, due to the nature of 5' to 3' DNA replication. Therefore, the poly-G region would eventually be removed revealing the true telomere repeats and allowing telomerase to extend the chromosome once again.

In a worst case scenario, rather than degrade the poly-G region the cell undergoes recombination between poly-G regions on multiple chromosomes, leading to either massive chromosomes or circular chromosomes. However, I'm sure these cells would die with some kind of massive mitotic failure.

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