Helicases are ubiquitous and conserved enzymes that unwind duplex nucleic acids and translocate along nucleic acid strands by utilizing the energy from the hydrolysis of nucleoside triphosphates. Based on their substrate preference/specificity, these enzymes are classified as DNA or RNA helicases, although some can unwind both RNA and DNA as well as RNA: DNA hybrids. Since DNA helicases play important roles in DNA replication, repair, and recombination, their deficiency can lead to DNA damage and genome instability, further contributing to human diseases, including premature aging, genetic disorders and cancer. Comparatively, RNA helicases participate in all aspects of RNA metabolism, including transcription, editing, export, degradation, mRNA splicing, R-loop resolution, and rRNA processing. Accordingly, RNA helicases are tightly linked to human health, and their deficiency can result in neurological disorders, cancer, aging, and infections caused by viruses, bacteria and fungi.

A great amount of literature has been published over the past few decades on novel helicases and on new roles of known helicases, thus revealing the mechanisms and the biological relevance of this important class of enzymes.
However, several areas remain largely unclear, including the involvement of helicases in nucleic acids metabolism, the regulation of their activities in diverse cellular processes, and their impact in human health. The human genome encodes at least 95 helicases, including 64 RNA and 31 DNA helicases. These enzymes are equipped with other functional domains (or in complex with their partners/cofactors) in addition to the conserved helicase motifs, allowing them to participate in diverse cellular activities. Thus, our knowledge of the biochemical properties and cellular functions of many helicases is still limited. In addition, mutations and/or abnormal expression of helicase genes are closely associated with many genetic disorders, neurodegenerative diseases and cancers. However, the mechanisms underlying these clinical phenotypes are not completely understood.
In this Research Topic, we aim to provide a comprehensive overview of the current understanding of helicase functions and their roles in guarding human health and also to explore potential therapeutic interventions by targeting relevant processes that are affected by helicase mutation/loss/dysregulation in diseases.

As part of this Research Topic, we are interested in original studies and review articles covering fundamental aspects of helicases including, but not limited to:
• Biochemical activities and regulatory mechanisms of helicase action.
• Mutational studies of Helicases and the consequential effects on its biological functions.
• Helicases and their roles in genetic disorders, neurodegenerative diseases and tumorigenesis using relevant model systems.
• Translational research targeting helicases for the management and treatment of diseases.

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Frontiers in Molecular Biosciences

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