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

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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.

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.

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)

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.

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.

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

Sources: POLD1: DNA polymerase delta catalytic subunit (human) (UniProt, 2026); 6TNY: Processive human polymerase delta holoenzyme (RCSB Protein Data Bank, 2026); DNA strand elongation (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.