helicase

Helicase is an enzyme that unwinds double-stranded nucleic acids (DNA or RNA) using energy from ATP hydrolysis. By separating base pairs, helicases create single-stranded templates necessary for replication, repair, recombination, transcription, and RNA processing. Helicases are found in all organisms and in many viruses, and they act in concert with other proteins as part of larger molecular machines such as replisomes and spliceosomes.

Most helicases are hexameric ring-shaped or monomeric motors belonging to several superfamilies, with SF1 and SF2 being the best characterized for DNA- and RNA-dependent unwinding. They translocate along one nucleic acid strand and destabilize the duplex ahead of them. Helicases carry conserved ATPase motifs, including Walker A and B; DEAD-box and related helicases belong to SF2 and are especially important for RNA remodeling. They exhibit directional polarity, moving 5' to 3' or 3' to 5' along the nucleic acid.

Biological roles and examples: In bacteria, DnaB functions as the primary replicative DNA helicase; in eukaryotes, the MCM2-7 complex acts as the core replicative helicase, loaded by Cdc6/Cdt1 and activated by associated factors. Other helicases participate in repair (e.g., UvrD), transcription, and RNA processing (e.g., DEAD-box helicases such as Ded1). Viral helicases such as HCV NS3 also play essential roles in replication.

Clinical relevance: Mutations in certain helicases, especially the RecQ family (BLM, WRN, RECQL4), are linked to genetic disorders with cancer predisposition and premature aging; helicases are also explored as targets for antiviral and anticancer therapies.