Helicase

Helicase is an essential enzyme that unwinds and separates double-stranded DNA or RNA by breaking the hydrogen bonds between complementary strands. This process is critical for DNA replication, transcription, repair, and recombination.


Key Characteristics:

  • Motor protein: Uses energy from ATP hydrolysis to move along nucleic acid strands.
  • Works in a 5′ → 3′ or 3′ → 5′ direction, depending on the helicase type.
  • Creates single-stranded templates needed for polymerase enzymes.

Functions of Helicase:

Biological ProcessRole of Helicase
DNA replicationUnwinds DNA at the replication fork so DNA polymerase can synthesize new strands.
TranscriptionHelps RNA polymerase access the DNA template.
DNA repairUnwinds damaged regions to allow repair enzymes access.
RecombinationAssists in separating DNA strands during genetic exchange.

Examples of Helicases:

Organism/ContextHelicase NameFunction
E. coliDnaB helicaseMain helicase at the bacterial replication fork
HumansMCM complexHelicase complex that unwinds DNA during replication
NER pathwayXPB and XPD (part of TFIIH)Unwind DNA around damage sites in nucleotide excision repair
RNA processesDDX family helicasesInvolved in RNA splicing, translation, and transport

Mechanism of Action:

  1. Helicase binds to DNA at the replication origin or repair site.
  2. It uses ATP hydrolysis to power movement along one strand.
  3. As it moves, it breaks hydrogen bonds between base pairs.
  4. This opens the DNA double helix, forming single-stranded regions.

Clinical Relevance:

  • Werner syndrome and Bloom syndrome: Caused by mutations in human DNA helicases, leading to premature aging and genomic instability.
  • Cancer: Helicase malfunction can cause replication stress and mutations, contributing to cancer development.
  • Antiviral targets: Viral helicases (e.g., in hepatitis C, SARS-CoV-2) are drug targets for antiviral therapies.

Summary Table:

PropertyDescription
Type of EnzymeATP-dependent motor protein
SubstrateDNA or RNA
ActionUnwinds double-stranded nucleic acids
Key ProcessesReplication, transcription, repair, recombination
Directionality5′→3′ or 3′→5′ depending on helicase
Clinical ImportanceLinked to aging disorders, cancer, and antiviral drug targets