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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# DNA polymerases

DNA polymerases copy DNA by adding nucleotides one by one to the 3' end of the new strand, following the template strand.

Updated 2026-11-01

Loading the 3D model…

## Key facts

- Reaction: (DNA)n + dNTP → (DNA)n+1 + PPi; pyrophosphate hydrolysis makes the step irreversible.
- Always 5'→3', always on a primer with a free 3'-OH, always following a template.
- Eukaryotes: α (with primase, starts), δ (lagging strand), ε (leading strand), β (base excision repair), γ (mitochondria).
- δ and ε proofread with their 3'→5' exonuclease; α and β do not.
- Bacteria: pol III replicates, pol I removes primers with its 5'→3' exonuclease and fills in.

**Also called**
Pol δ, Pol ε, Pol α-primase

**EC number**
[2.7.7.7](https://www.enzyme-database.org/query.php?ec=2.7.7.7)

**Genes**
POLA1, POLD1, POLE, POLB, POLG

**Structure (PDB)**
[6TNY](https://www.rcsb.org/structure/6TNY)

## Regulation

- Processivity: the PCNA clamp (loaded by RFC) keeps δ and ε on the DNA for thousands of bases.
- dNTP supply: ribonucleotide reductase and its allosteric control keep the four dNTPs balanced.
- Translesion polymerases (η, κ, ι, ζ) are switched on by PCNA ubiquitination to bypass lesions, at the cost of more errors.

## Inhibitors and toxins

- Cytarabine and gemcitabine (triphosphates: chain termination or stalling)
- Aciclovir and ganciclovir (herpesvirus polymerase)
- Antiretroviral nucleoside analogues (on HIV reverse transcriptase; some damage mitochondrial pol γ)
- Aphidicolin (pol α, δ and ε; laboratory use)

## Clinical notes

- Variants in the exonuclease domain of POLE and POLD1 cause polyposis and colorectal and endometrial cancers with huge numbers of mutations (ultramutated phenotype).
- Mitochondrial toxicity of some older antiretrovirals (neuropathy, lactic acidosis) is explained by pol γ inhibition.
- POLG mutations cause mitochondrial diseases such as Alpers syndrome.

## Related conditions

- [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/)

## Related

- [DNA replication: the replication fork](https://durgical.com/en/biochemistry/topics/dna-replication-the-replication-fork/)
- [DNA helicases](https://durgical.com/en/biochemistry/enzymes/dna-helicases/)
- [DNA repair](https://durgical.com/en/biochemistry/topics/dna-repair/)
- [Polymerase chain reaction (PCR)](https://durgical.com/en/biochemistry/topics/polymerase-chain-reaction/)
- [DNA sequencing](https://durgical.com/en/biochemistry/topics/dna-sequencing/)
- [Ribonucleotide reductase](https://durgical.com/en/biochemistry/enzymes/ribonucleotide-reductase/)
- [Drugs acting on nucleotide metabolism](https://durgical.com/en/biochemistry/topics/drugs-acting-on-nucleotide-metabolism/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which eukaryotic DNA polymerase mainly makes the lagging strand?

Pol δ, bound to PCNA; pol ε mainly handles the leading strand.

## Which activity lets a polymerase correct its own mistakes?

The 3'→5' exonuclease (proofreading), which removes the last mispaired nucleotide.

## Why does aciclovir hit herpesvirus and spare human cells?

Only the viral thymidine kinase phosphorylates it well, and its triphosphate prefers the viral polymerase, where it ends the chain.

## What does the 3D model 6TNY show, and which ligand marks the active site?

Human pol δ with PCNA on DNA; the incoming dTTP (TTP) marks where the nucleotide is added.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [POLD1: DNA polymerase delta catalytic subunit (human)](https://www.uniprot.org/uniprotkb/P28340/entry) (UniProt, 2026); [6TNY: Processive human polymerase delta holoenzyme](https://www.rcsb.org/structure/6TNY) (RCSB Protein Data Bank, 2026); [DNA strand elongation](https://reactome.org/PathwayBrowser/#/R-HSA-69190) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.

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