Telomeres: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Telomere length: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Telomeres are caps made of the sequence TTAGGG, repeated many times, at the ends of chromosomes. They become shorter with each cell division and are lengthened again by telomerase in germ and stem cells.

The pathway step by step

1. Chromosome end → Telomere The telomere is this cap: the same short letter sequence TTAGGG, repeated thousands of times. It carries no building instructions but seals the end. Source 1
2. Telomere → Shelterin · TRF1, TRF2, POT1 Six proteins, together called shelterin, bind to these repeats. TRF1, TRF2 and POT1 are among them. Source 1
3. Shelterin → T-loop Shelterin folds the outermost stretch back into a loop and tucks it into the double strand. The end is thus hidden and not treated as a break. Source 1
4. DNA replication → Shorter telomere DNA polymerase At the very end of the lagging strand there is no room for this starter piece. The telomere therefore becomes a little shorter with every copy. Source 2
5. Shorter telomere → Division stop · p53 pathway When a telomere is very short, the cell recognises the end as a DNA break. Via the p53 signalling pathway it stops dividing and remains in place as a cell. Source 4
6. Shorter telomere → Lengthened telomere Telomerase · RNA template (TERC) Telomerase carries its own RNA as a template and adds new TTAGGG units. It is active in germ and stem cells, and barely active in most other cells. Source 3
7. Lengthened telomere → Telomere length Laboratories usually determine the average telomere length in white blood cells, by PCR or under the microscope. It results from shortening and lengthening combined. Source 5

Cofactors in this pathway

• Deoxynucleotides — Building blocks from which telomerase assembles the TTAGGG units Source 3
• Magnesium — Two magnesium ions in the active site of polymerases link the building blocks Source 6In the ORY catalogue as a laboratory value: Magnesium
• Iron — Metal of ribonucleotide reductase, which forms deoxynucleotides Source 7In the ORY catalogue as a laboratory value: Eisen
• Folate — As 5,10-methylene-THF, supplies the methyl group for thymidine, a DNA building block Source 8In the ORY catalogue as a laboratory value: Folsäure
• Serine — Main source of the one-carbon units that enter thymidine via folate Source 8In the ORY catalogue as a laboratory value: Serin

Sources

1. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 2005 · PubMed 16166375
2. Bonnell E, Pasquier E, Wellinger RJ. Telomere Replication: Solving Multiple End Replication Problems. Front Cell Dev Biol 2021 · PubMed 33869233
3. Wang Y, Sušac L, Feigon J. Structural Biology of Telomerase. Cold Spring Harb Perspect Biol 2019 · PubMed 31451513
4. d'Adda di Fagagna F, Reaper PM, Clay-Farrace L et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003 · PubMed 14608368
5. Fasching CL. Telomere length measurement as a clinical biomarker of aging and disease. Crit Rev Clin Lab Sci 2018 · PubMed 30265166
6. Yang W, Lee JY, Nowotny M. Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity. Mol Cell 2006 · PubMed 16600865
7. Nordlund P, Reichard P. Ribonucleotide reductases. Annu Rev Biochem 2006 · PubMed 16756507
8. Ducker GS, Rabinowitz JD. One-Carbon Metabolism in Health and Disease. Cell Metab 2017 · PubMed 27641100

Related pathways

• Methylation: methionine and homocysteine — Magnesium, Folsäure
• Citric acid cycle — Magnesium, Eisen
• Estradiol — Magnesium, Eisen
• Glycine and serine — Magnesium, Folsäure
• Dopamine, noradrenaline, adrenaline — Magnesium, Eisen

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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