Question

Saccharomyces cerevisiae telomeres consist of a continuous ~ 350 bp tract of the repeat TG₃. If the average Okazaki fragment in a yeast cell is 200 nucleotides, what is the maximum number of times that a yeast cell can replicate before its telomeres are gone?

Answer 1

Hello!

So for this question you have to manage DNA replication very well. Just to remember, DNA replication is the process by which a cell duplicates its DNA in a semiconservative way, that is, both "old" strands of the DNA will be split and a new strand complementary to each old strand will be synthesized. The enzyme responsible for this is the DNA polymerase, which reads a strand in 3´-5´direction, synthesizing the new strand in the 5´-3´direction.

Because of this mechanism, there can be Differentiated two new strands: a leading strand which is synthesized in a complete DNA strand. And a lagging strand, which is formed by the union of the okazaki fragments.

When DNA polymerase reaches the end of the chromosome, the leading strand is synthesized up to the end of the chromosome. BUT, the lagging strand will leave a gap because a new primer of RNA couldn´t be added. As there is a single strand overhang (which corresponds to the gap that couldn´t be filled by DNA polymerase), this overhang is susceptible for degradation by single strand-DNA degrading enzymes, which can cause a loss in the chromosome for each duplication event, that is for each time the cell divides.

However, there is an enzyme that prevents this to happen, TELOMERASE. This enzyme, depicted in green in the figure, can extend the old strand giving enough space for the primase enzyme to put a new RNA primer in the telomerase synthesized DNA, allowing the DNA polymerase to complete the replication of the entire genome.

By the way: telomeres are the ends of the chromosome and they dont have "vital" information for the cell.

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So, to solve this problem you have to assume two things:

1- the replication origins are always in the same place.

2- telomerase enzyme is not functional in this yeast (if it is functional there will not be any problem in each replication step).

The best situation for this yeast (cell #0) is that the RNA primer is made just at the end of the old strand. The last RNA primer is degraded and is not replaced by DNA, so the new daughter cell (cell #1) will have shortened it telomere in 10 bp (340 bp).

When this cell duplicates its DNA, the last Okazaki fragment of the mother cell cannot be synthesized, as there is no place for the RNA primase enzyme because there is 10 bp less. So, the single strand that will be degraded is 200 bp long (190 bp and 10 bp of the degraded RNA primer). The telomere of the new cell (cell #2) will be 340 bp - 200 bp = 140 bp.

When cell #2 duplicates, the same will happen. So, cell #3 will have a telomere of 140 bp - 200 bp = -60 bp. This means that cell #3 will have 60 bp of VITAL DNA lost. So, cell #3 is not viable.

Then, this yeast will only be able to replicate 2 times. The third replication will not give a viable cell.