What is a Helicase?

A helicase is an enzyme that unzips joined strands of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). It usually moves in one direction down a double-stranded DNA molecule or self-bound RNA molecule, breaking the hydrogen bonds between the complementary nucleotide base pairs. Helicase enzymes are important for the cellular processes of DNA replication and repair, transcription of DNA to RNA, protein translation, and the creation of ribosomes.

There are many different types of helicase enzymes, including 24 different helicases in the human body. Each has a slightly different structure and method of operation. Some work as monomers, or single-unit enzymes, while others form dimers or even hexamers, combining multiple protein subunits for optimal function. All helicases share at least some degree of similarity in their amino acid sequence, and these similar areas are thought to be involved in the binding of the DNA or RNA strand or the binding and hydrolysis of adenosine triphosphate (ATP). These common sequence motifs have aided in the classification of helicases into five major families.

The function of a helicase varies depending on its specific structure and technique for unwinding. Some are active, utilizing ATP to unwind the strands, while others are passive and do not require energy to function. Since DNA and RNA molecules combine and remain connected through hydrogen bonds, many helicases will use molecules of ATP to actively break these bonds. These enzymes will have an ATP binding site that will enable them to hydrolyze ATP to gain the energy needed to break the hydrogen bonds. The breakdown of ATP will often propel the enzyme down the DNA or RNA strand, making its motion unidirectional and allowing it to prevent the recently separated strands from recombining.

Other helicase enzymes do not use active energetic methods to separate the nucleotide base pairs. Instead, they attach to the DNA or RNA strands and wait until local energetic fluctuations and movement changes partially twist the strands apart. They then translocate and bind in the newly formed gap, preventing the strands from rejoining. This mechanism is generally slower, as it is dependent upon chance and random movements for unwinding, rather than a direct, controlled mechanism.

Some RNA helicase enzymes will use a different mechanism for binding and unwinding. While many RNA helicases act in a manner similar to DNA helicase, others will bind with a single stranded segment of RNA and will also require ATP binding. These helicases will not actually hydrolyze the ATP or derive energy from it, but the ATP is necessary for a change in shape that will activate the enzyme.