outline the role of telomeres in preventing the loss of genes from the ends of chromosomes during DNA replication

Published by Patrick Mutisya · 14 days ago

Cambridge A-Level Biology 9700 – Replication and Division of Nuclei and Cells

Replication and Division of Nuclei and Cells

Learning Objective

Outline the role of telomeres in preventing the loss of genes from the ends of chromosomes during DNA replication.

Key Concepts

  • DNA polymerase can only add nucleotides to an existing 3′‑OH group.

  • During each S‑phase, the very ends of linear chromosomes cannot be fully replicated – the “end‑replication problem”.

  • Telomeres are specialised repetitive DNA sequences that protect chromosome ends.

  • Telomerase is a ribonucleoprotein enzyme that extends telomeres.

The End‑Replication Problem

When the replication fork reaches the end of a linear chromosome, the RNA primer that initiates synthesis of the lagging strand cannot be replaced by DNA because there is no upstream 3′‑OH. Consequently, a short segment of DNA is lost each cell division.

Mathematically, if \$L\$ is the length of DNA lost per division, after \$n\$ divisions the total loss is \$nL\$.

Structure of Telomeres

Telomeres consist of short, tandem repeats (e.g., in humans: TTAGGG) followed by a specialised protein complex (shelterin) that stabilises the structure.

Function of Telomeres

FunctionExplanation
Buffer against DNA lossRepetitive sequences are sacrificed first, preserving coding regions.
Prevent chromosome end‑to‑end fusionsProtein caps hide the ends from DNA damage sensors.
Regulate cellular lifespanProgressive shortening signals senescence or apoptosis.

Role of Telomerase

Telomerase carries its own RNA template, allowing it to add telomeric repeats to the 3′ end of the DNA strand:

\$\text{DNA}{\text{new}} = \text{DNA}{\text{old}} + \text{(TTAGGG)}_n\$

In most somatic cells telomerase activity is low, leading to gradual telomere shortening. In germ cells, stem cells, and many cancer cells, telomerase is active, maintaining telomere length and enabling indefinite division.

Consequences of Telomere Shortening

  1. Activation of DNA damage checkpoints.

  2. Induction of cellular senescence (growth arrest).

  3. Triggering of apoptosis if damage is irreparable.

  4. Potential genomic instability if critically short telomeres fuse.

Summary

Telomeres act as protective caps that absorb the inevitable loss of DNA at chromosome ends during replication. By providing a non‑coding buffer zone, they safeguard essential genes and maintain chromosome integrity across many cell divisions. Telomerase counteracts shortening in specific cell types, linking telomere dynamics to ageing, stem‑cell function, and cancer.

Suggested diagram: A schematic showing a replication fork approaching a chromosome end, the formation of a telomere, and the action of telomerase adding repeats.