Abstract
G-quadruplexes (G4s) are stable non-canonical secondary structures formed by G-rich DNA or RNA sequences. They play various regulatory roles in many biological processes. It is commonly agreed that G4 unwinding helicases play key roles in G4 metabolism and function, and these processes are closely related to physiological and pathological processes. In recent years, more and more functional and mechanistic details of G4 helicases have been discovered; therefore, it is necessary to carefully sort out the current research efforts. Here, we provide a systematic summary of G4 unwinding helicases from the perspective of functions and molecular mechanisms. First, we provide a general introduction about helicases and G4s. Next, we comprehensively summarize G4 unfolding helicases in humans and their proposed cellular functions. Then, we review their study methods and molecular mechanisms. Finally, we share our perspective on further prospects. We believe this review will provide opportunities for researchers to reach the frontiers in the functions and molecular mechanisms of human G4 unwinding helicases.
Highlights
Specialty section: This article was submitted to Protein Biochemistry for Basic and Applied Sciences, a section of the journal Frontiers in Molecular Biosciences
Helicases are involved in almost all aspects of nucleic acid functions and metabolisms, such as DNA replication, DNA recombination, RNA transcription, translation, DNA repair, telomere maintenance, ribosome biogenesis, pre-mRNA splicing, viral RNA sensing, and micro RNA (miRNA) biogenesis (Lohman and Bjornson, 1996; Jankowsky et al, 2011)
The first helicase was isolated from HeLa cells in 1990 (Tuteja et al, 1990), and a total of 95 non-redundant helicases including 64 RNA helicases and 31 DNA helicases were identified (Umate et al, 2011), a few helicases can act on both RNA and DNA (Creacy et al, 2008; Talwar et al, 2017)
Summary
Helicases are ubiquitous motor proteins that unwind the hydrogen bonds between nucleic acids by coupling the chemical energy from nucleoside triphosphates (NTPs) (Lohman and Bjornson, 1996). The first helicase was isolated from HeLa cells in 1990 (Tuteja et al, 1990), and a total of 95 non-redundant helicases including 64 RNA helicases and 31 DNA helicases were identified (Umate et al, 2011), a few helicases can act on both RNA and DNA (Creacy et al, 2008; Talwar et al, 2017). Because of their importance, helicases are closely related to age-related diseases, such as cancer. Besides the canonical duplex DNA or RNA, helicases are able to unfold other secondary structures such as Holliday junction, double Holliday junction, and G4s (Brosh, 2013)
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