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
- Genes
- TOP1, TOP2A, TOP2B
- Structure (PDB)
- 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
Related
- Bacterial DNA gyrase (target of fluoroquinolones)
- DNA replication: the replication fork
- DNA helicases
- DNA structure and chromatin
- 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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: TOP1: DNA topoisomerase 1 (human) (UniProt, 2026); TOP2A: DNA topoisomerase 2-alpha (human) (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 (RCSB Protein Data Bank, 2026); 3QX3: Human topoisomerase IIbeta in complex with DNA and etoposide (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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