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

# Topoisomerases (I and II)

Topoisomerases cut and rejoin DNA to remove the twists that build up when it opens; they are the target of several anticancer drugs.

Updated 2026-11-01

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## Key facts

- Type I: cuts one strand, lets the other rotate and rejoins it; uses no ATP. Changes the linking number by 1.
- Type II: cuts both strands, passes another double helix through the gap and seals; uses ATP. Changes the linking number by 2 and unlinks entangled chromosomes.
- The enzyme stays attached to DNA by a covalent phosphotyrosine bond while the DNA is cut.
- Topoisomerase 'poisons' stabilise the cut complex and turn the enzyme into a source of breaks.
- Human topo I: irinotecan and topotecan (camptothecins). Topo II: etoposide, doxorubicin. In bacteria: gyrase and topo IV, targets of fluoroquinolones.

**Also called**
Topo I, Topo II

**EC number**
[5.6.2.1 / 5.6.2.2](https://www.enzyme-database.org/query.php?ec=5.6.2.1 / 5.6.2.2)

**Genes**
TOP1, TOP2A, TOP2B

**Structure (PDB)**
[1K4T](https://www.rcsb.org/structure/1K4T)

## Regulation

- Topo IIα is abundant in dividing cells (S/G2/M phase), so fast-growing tumours are more sensitive.
- Topo IIβ is expressed in non-dividing cells and takes part in transcription.

## Inhibitors and toxins

- Camptothecins: irinotecan, topotecan (topo I)
- Etoposide (topo II)
- Anthracyclines: doxorubicin, daunorubicin (topo II, also intercalators)
- Fluoroquinolones (bacterial gyrase and topo IV; see DNA gyrase)

## Clinical notes

- Anti-topoisomerase I antibodies (anti-Scl-70) are linked to diffuse systemic sclerosis.
- Etoposide and anthracyclines can cause secondary leukaemias with KMT2A (MLL) rearrangements.
- Doxorubicin cardiotoxicity is partly linked to topo IIβ in heart muscle.

## Drugs that act here

- [Doxorubicin](https://durgical.com/en/pharmacology/doxorubicin/)
- [Daunorubicin](https://durgical.com/en/pharmacology/daunorubicin/)
- [Epirubicin](https://durgical.com/en/pharmacology/epirubicin/)
- [Idarubicin](https://durgical.com/en/pharmacology/idarubicin/)
- [Etoposide](https://durgical.com/en/pharmacology/etoposide/)
- [Irinotecan](https://durgical.com/en/pharmacology/irinotecan/)
- [Topotecan](https://durgical.com/en/pharmacology/topotecan/)
- [Dexrazoxane](https://durgical.com/en/pharmacology/dexrazoxane/)

## Related

- [Bacterial DNA gyrase (target of fluoroquinolones)](https://durgical.com/en/biochemistry/enzymes/bacterial-dna-gyrase/)
- [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 structure and chromatin](https://durgical.com/en/biochemistry/topics/dna-structure-and-chromatin/)
- [Transcription](https://durgical.com/en/biochemistry/topics/transcription/)

## Test yourself

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

## How do topoisomerase I and II differ?

Type I cuts one strand and uses no ATP; type II cuts both, passes another helix through the cut and uses ATP.

## How do topoisomerase 'poisons' such as etoposide kill cells?

They stabilise the cut enzyme–DNA complex; the cuts are not resealed and become lethal breaks.

## Which anti-topoisomerase autoantibody is typical of diffuse systemic sclerosis?

Anti-Scl-70, directed against topoisomerase I.

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

Sources: [TOP1: DNA topoisomerase 1 (human)](https://www.uniprot.org/uniprotkb/P11387/entry) (UniProt, 2026); [TOP2A: DNA topoisomerase 2-alpha (human)](https://www.uniprot.org/uniprotkb/P11388/entry) (UniProt, 2026); [1K4T: HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX](https://www.rcsb.org/structure/1K4T) (RCSB Protein Data Bank, 2026); [3QX3: Human topoisomerase IIbeta in complex with DNA and etoposide](https://www.rcsb.org/structure/3QX3) (RCSB Protein Data Bank, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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