Helicases

Helicases are a diverse group of enzymes that unwind double-stranded nucleic acids, using energy from ATP hydrolysis to separate the two strands. This activity is essential for processes such as DNA replication, transcription, repair, recombination, and RNA processing. Helicases can move along nucleic acids in a defined direction, typically 5’ to 3’ or 3’ to 5’, and they often act at or near replication forks, transcription bubbles, or repair intermediates.

Many helicases are helicase superfamilies SF1 and SF2, which include both DNA and RNA helicases. These enzymes typically contain two RecA-like ATPase domains that coordinate ATP binding and hydrolysis to drive conformational changes and translocation along a nucleic acid strand. Some helicases operate as monomers or dimers, while others form ring-shaped hexamers that encircle a single strand and unwind duplexes by feeding the opposite strand through a central channel. Mechanistic models include inchworm-like movement and sequential ATP hydrolysis around a hexameric ring.

Biological roles of helicases are wide-ranging. In replication, replicative helicases such as the MCM complex in eukaryotes and DnaB in bacteria unwind the parental DNA to allow polymerases to copy the genome. In repair and recombination, helicases resolve structured DNA or remodel DNA–protein complexes. RNA helicases, including many DEAD-box proteins, remodel RNA structures and assist in RNA splicing, ribosome assembly, and translation.

Defects in helicases are linked to genomic instability and disease, underscoring their essential function in maintaining nucleic acid metabolism.