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DNA helicases !

Helicases are motors that separate the two DNA strands using ATP; they open the replication fork and help repair DNA.

Updated 2026-11-01

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Key facts

  • They break the hydrogen bonds between bases using energy from ATP hydrolysis.
  • The eukaryotic replicative helicase is the MCM2-7 ring, active as the CMG complex (Cdc45-MCM-GINS). In bacteria: DnaB.
  • RecQ helicases: BLM (Bloom syndrome), WRN (Werner syndrome, premature ageing), RECQL4 (Rothmund-Thomson).
  • TFIIH holds two helicases (XPB, XPD) that open DNA in transcription and in nucleotide excision repair.
  • Their loss causes genome instability and cancer predisposition.
Also called
MCM helicase, RecQ helicases (BLM, WRN)
EC number
5.6.2.4
Genes
MCM2–MCM7, BLM, WRN, RECQL4
Structure (PDB)
4O3M

Regulation

  • MCM is loaded inactive in G1 (licensing) and only activated in S by CDK and DDK kinases.
  • BLM forms the 'dissolvasome' with topoisomerase IIIα, RMI1 and RMI2, which undoes double Holliday junctions without crossing over.
  • RPA proteins coat the single strand the helicase leaves behind.

Inhibitors and toxins

  • No drugs in clinical use; WRN inhibitors under study for microsatellite-unstable tumours

Clinical notes

  • In Bloom syndrome, loss of BLM greatly increases sister chromatid exchanges, a diagnostic sign.
  • XPD (ERCC2) mutations can give xeroderma pigmentosum or trichothiodystrophy depending on how they affect repair and transcription.
  • Microsatellite-unstable tumour cells depend on WRN to survive (synthetic lethality).

Test yourself

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

What energy source do helicases use to separate DNA?

ATP (or another NTP) hydrolysis, which moves the enzyme along the strand.

Which helicase is missing in Bloom syndrome, and what cytogenetic sign does it give?

The RecQ helicase BLM; there are many more sister chromatid exchanges.

What is the active eukaryotic replicative helicase called?

The CMG complex: Cdc45, the MCM2-7 ring and GINS.

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

Sources: BLM: RecQ-like DNA helicase BLM (human) (UniProt, 2026); MCM6: DNA replication licensing factor MCM6 (human) (UniProt, 2026); 4O3M: Ternary complex of Bloom's syndrome helicase (RCSB Protein Data Bank, 2026); DNA Replication (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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