Telomeres and the end-replication problem
About this app
Why linear chromosomes get shorter with every copy: at the end the gap left by the last RNA primer remains because there is no 3′-OH in front of it. Telomeres made of TTAGGG shrink over many divisions down to the Hayflick limit; telomerase extends them with its own RNA template. Plus a comparison with circular bacterial DNA.
With explain mode: an AI tutor walks you through the app, points out what matters in the scene and answers your questions.
The end-replication problem
DNA polymerase extends a strand only in the 5′ to 3′ direction and needs a free 3′-OH, supplied by an RNA primer. At the end of a linear chromosome the last primer is removed, but the gap cannot be filled because there is no 3′-OH in front of it. The new strand is shorter, the old one forms a 3′ overhang. A piece is lost at every division. Telomeres made of many repeats of TTAGGG buffer this loss; when they are too short, the cell stops dividing (Hayflick limit). Telomerase extends the ends with its own RNA template.
What the app shows
Four views: replication at the chromosome end step by step with leading strand, Okazaki fragments and primers; telomere length over up to 80 divisions; telomerase writing repeat after repeat with its template 3′-CAAUCCCAAUC-5′; and a comparison with circular bacterial DNA, which has no end. In the model a telomere is 10,000 base pairs long, 5,000 is critical.
Things to try
Step through the five stages at the chromosome end and find the strand that gets shorter. Set the loss per division between 50 and 200 base pairs and read off when the Hayflick limit is reached. Switch telomerase on and compare how long the cell can keep dividing. The ring view shows why bacteria do not have this problem.
Frequently asked questions
- What is the end-replication problem?
- At the end of a linear chromosome, DNA polymerase cannot fill the gap of the last RNA primer because there is no free 3′-OH in front of it. The newly made strand therefore gets a little shorter with each replication, and the chromosome end shrinks with every cell division.
- What are telomeres and what are they for?
- Telomeres are the ends of linear chromosomes. In humans they consist of thousands of repeats of the sequence TTAGGG and carry no genes. They buffer the loss at each division. When they become too short, the cell stops dividing; in humans after about 40 to 60 divisions (Hayflick limit).
- How does telomerase work?
- Telomerase is a reverse transcriptase with its own RNA template. Part of the template pairs with the overhanging 3′ end of the old strand, the rest serves as a template for adding another TTAGGG repeat. Then it moves on. Primase and polymerase fill in the opposite strand. It is active in stem cells, germ cells and most tumours.
- What can I set in the Telomeres app?
- You step through replication at the chromosome end, set the number of divisions and the loss per division, switch telomerase on or off, follow its working steps and compare a linear chromosome with circular DNA.
Subject: Biology (Gymnasium)
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