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What’s a helicase?

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Helicase enzymes break hydrogen bonds between nucleotide base pairs in DNA or RNA. There are many types, with different structures and methods of operation. Some use ATP to actively break bonds, while others attach to strands and wait for distortion. RNA helicases may require ATP for activation.

A helicase is an enzyme that unzips joined strands of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). It usually moves in one direction along a double-stranded DNA molecule or self-linked RNA molecule, breaking the hydrogen bonds between complementary nucleotide base pairs. Helicase enzymes are important for the cellular processes of DNA replication and repair, transcription of DNA into 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 function 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 DNA or RNA strand binding or in 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 according to its specific structure and unwinding technique. Some are active, using ATP to unwind threads, while others are passive and require no energy to function. Because DNA and RNA molecules combine and remain linked through hydrogen bonds, many helicases will use ATP molecules to actively break these bonds. These enzymes will have an ATP binding site that will allow them to hydrolyze ATP to obtain the energy needed to break the hydrogen bonds. Breaking down ATP will often push the enzyme along the DNA or RNA strand, making its movement unidirectional and allowing it to prevent recombination of the recently separated strands.

Other helicase enzymes do not use active energy methods to separate nucleotide base pairs. Instead, they attach themselves to DNA or RNA strands and wait for local energy fluctuations and motion changes to partially distort the strands. They then translocate and bind themselves in the newly formed space, preventing the threads from rejoining. This mechanism is generally slower, as it depends on chance and random movements for unwinding, rather than a direct and controlled mechanism.

Some RNA helicase enzymes will use a different mechanism to bind and unwind. While many RNA helicases act similar to DNA helicases, others will bind to a single stranded segment of RNA and also require ATP to bind. These helicases won’t actually hydrolyze ATP or get energy from it, but ATP is needed for a shape change that will activate the enzyme.

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