Lesson 3 of 6 / DNA replication and gene expression
The end-replication problem
Why can the last RNA primer leave an unfillable gap?
In this lesson: Explain shortening at linear chromosome ends during replication.
About 6 min
The key ideaAfter a terminal primer is removed, no upstream 3-prime end may remain to fill its gap, so a linear chromosome end can shorten.
Explore the idea
Can polymerase fill this gap?
Orange is the RNA primer at the 5-prime end of a newly synthesised fragment; blue DNA extends to its right. The primer is part of that new strand, not a bridge between the two strands. Predict what can happen when it is removed.
The direction of synthesis is rightwards in both comparisons. Telomeric repeats help buffer linear ends; telomerase can extend telomeric DNA in certain cells. A circular chromosome has no equivalent terminal geometry.
Explanation
Replication enzymes can replace an internal RNA primer because an adjacent DNA fragment supplies an extendable 3-prime end. At the end of a linear chromosome, removing the terminal lagging-strand primer can leave no such upstream DNA end. DNA polymerase cannot start from nothing to replace it.
The resulting daughter DNA can therefore be shorter at one end. Telomeres are repetitive DNA-protein structures at chromosome ends that help protect coding regions and prevent ends being treated as ordinary breaks. They do not mean that DNA polymerase suddenly reverses its synthesis direction.
The problem arises from linearity and the enzyme's need for a primer. A circular bacterial chromosome has no equivalent terminal end, although it still needs primers and careful completion of replication. Do not claim all circular DNA replication is primer-free.
Telomerase can extend telomeric DNA in certain cells, using an internal RNA template, allowing conventional enzymes to complete more of the complementary strand. This provides explanatory context; the central required reasoning is why a terminal primer creates a problem. Telomere biology is not a simple one-number clock predicting a person's lifespan.
Step by step
- 1
Remove the terminal primer
Mark the remaining gap.
- 2
Search for a starting end
Ask where polymerase could attach the next nucleotide.
- 3
Compare linear and circular DNA
Only the linear model has the relevant terminal geometry.
Worked example
Work through the evidence
Why is an internal primer easier to replace than the last primer at a linear chromosome end?
One way to explain it
Internal replacement can extend from an adjacent upstream DNA 3-prime end. At the terminal gap that end is absent, and polymerase cannot initiate DNA synthesis de novo.
Why this answer works
- The issue is the location of an extendable end.
- It is not a shortage of complementary nucleotides.
Is this true? "Chromosome shortening occurs because helicase cuts off the last gene."
The end-replication problem follows from primer removal and polymerase directionality, not helicase excising a gene.