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DNA Replication Enzymes: Leading vs Lagging Strand for the MCAT
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DNA replication is semiconservative (each new double helix keeps one old strand) and bidirectional from each origin. DNA polymerase only adds nucleotides to a 3' end, so it builds 5' to 3'. That one rule explains why one strand is continuous and the other is made in pieces.
Enzymes in order
| Step | Enzyme or protein | Job |
|---|---|---|
| 1 | Helicase | Unwinds the helix at the origin, using ATP |
| 2 | Single-strand binding proteins | Keep separated strands from re-annealing |
| 3 | Topoisomerase (gyrase in bacteria) | Relieves supercoiling ahead of the fork |
| 4 | Primase | Makes a short RNA primer, giving polymerase a 3' end |
| 5 | DNA polymerase III (bacteria) | Extends the primer 5' to 3' |
| 6 | DNA polymerase I (bacteria) | Removes RNA primers, fills the gap with DNA |
| 7 | DNA ligase | Seals the remaining nick between fragments |
Leading vs lagging strand
- Leading strand: template runs so the polymerase follows the fork. Continuous synthesis, one primer.
- Lagging strand: template runs the other way, so synthesis goes away from the fork. It is made as Okazaki fragments, each needing its own primer, joined later by ligase.
Proofreading
DNA polymerase has 3' to 5' exonuclease activity. It backs up and removes a mismatched base before continuing. Mismatch repair fixes errors it misses.
Prokaryote vs eukaryote
| Prokaryote | Eukaryote | |
|---|---|---|
| Origins | One (oriC) | Many |
| Main polymerases | III (replication), I (primers) | Delta and epsilon (replication), alpha with primase |
| Okazaki fragments | Longer | Shorter |
| Ends | Circular chromosome, no end problem | Linear, telomerase extends telomeres |
Common traps
- Saying polymerase builds 3' to 5'. It reads the template 3' to 5' and builds 5' to 3'.
- Forgetting the primer. DNA polymerase cannot start from nothing.
- Mixing up polymerases I and III. III does most synthesis; I replaces primers.
One-minute recap
- Helicase unwinds, primase primes, polymerase extends, ligase seals.
- Leading is continuous; lagging is Okazaki fragments.
- Polymerase proofreads 3' to 5'.
Check yourself: 5-question mini-quiz
1. Which enzyme unwinds the DNA helix at the fork?
Helicase.
2. Why is the lagging strand made in fragments?
Polymerase only builds 5' to 3', so that strand is synthesized away from the fork in short pieces.
3. What does primase make?
A short RNA primer that gives polymerase a 3' end.
4. Which enzyme seals the nick between Okazaki fragments?
DNA ligase.
5. What enzyme extends telomeres in eukaryotes?
Telomerase.
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