The DEAH helicase DHX36 and its role in G-quadruplex-dependent processes

Abstract

DHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.

Multistep mechanism of G-quadruplex resolution during DNA replication

“…Another 5′-3′ DNA helicase, Regulator of telomere elongation helicase 1 (RTEL1), specifically suppresses telomeric G4 instability ( 20 ). Last, DEAH-box helicase 36 (DHX36) is a 3′-5′ helicase that exhibits an exceptional affinity for DNA G4 structures in vitro ( 21 ), but its biological function has been studied mostly in the context of RNA G4 processing ( 22 ). This helicase is essential for normal embryogenesis in mice ( 23 ), yet its role in DNA G4 unwinding in vivo remains unknown.…”

The RNA helicase DHX36–G4R1 modulates C9orf72 GGGGCC hexanucleotide repeat–associated translation

“…Given their potentially central role in G 4 C 2 repeats in C9 FTD/ALS pathogenesis, we explored factors responsible for G4 resolution within cells. One such enzyme, DHX36 (aliases: G4R1 and RHAU), is a member of the DExH-box family of helicases (39). DHX36 accounts for the majority of the tetramolecular G4 DNA and RNA helicase activity in HeLa cell lysates (40,41).…”

Action and function of helicases on RNA G-quadruplexes

“…Among other functions, at the DNA level DHX36 intervenes to resolve dG4s in gene promoters and thereby activating transcription [159] , [161] , [167] , [168] , [169] , [170] . The detailed discussion of DHX36 function within cells is reviewed elsewhere [171] . Like other DExD/H members [172] , [173] , DHX36 bears two tandem RecA-like domains making up the core helicase and ATPase functions, a winged-helix DNA/RNA-binding domain, a “ratchet” like domain (RL) and the DExD/H-specific β-barrel oligonucleotide- oligosaccharide-binding (OB) domain [174] ( Fig.…”