G-quadruplex unwinding helicases and their function in vivo

Abstract

The concept that G-quadruplex (G4) structures can form within DNA or RNA has been long known and extensively discussed. In recent years, accumulating evidences imply that G-quadruplex structures form Initially, inefficient regulation of G-quadruplex structures was mainly associated with genome instability. However, due to the location of G-quadruplex motifs and their evolutionary conservation, different cellular functions of these structures have been postulated (e.g. in telomere maintenance, DNA replication, transcription, and translation). Regardless of their function, efficient and controlled formation and unwinding are very important, because 'mis'-regulated G-quadruplex structures are detrimental for a given process, causing genome instability and diseases. Several helicases have been shown to target and regulate specific G-quadruplex structures. This mini-review focuses on the biological consequences of G4 disruption by different helicases .

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

“…The authors assumed that a general G4‐dependent mechanism could nevertheless underlie transcription changes in both cases and attributed the dissimilarity between the sets of activated genes to different substrate specificities of WRN and BLM helicases. Importantly, these helicases unwind G4s upon both replication and transcription . Although G4s are presumably most often formed in replication forks, the direct effects of persistent G4s on transcription are also possible.…”

“…Importantly, these helicases unwind G4s upon both replication and transcription. [29,30] Although G4s are presumably most often formed in replication forks, [28] the direct effects of persistent G4s on transcription are also possible. Upon helicase deficiency, G4s may stabilize R-loops or interfere with TF interactions and the R-loop/TF-dependent interactions with chromatin remodelers (Figure 2b).…”

“…Importantly, G4s have been detected at all phases of the cell cycle and their number is maximized during S‐phase, an observation that supports replication‐dependent G4 formation. Under normal conditions, G4s in replication forks and transcription‐associated G4s in R‐loops are unwound by specific helicases . Thus, G4s can be regarded as transient structures (Figure ) that nevertheless exert vital regulatory functions.…”

“…Under normal conditions, G4s in replication forks and transcription-associated G4s in R-loops are unwound by specific helicases. [29,30] Thus, G4s can be regarded as transient structures ( Figure 1) that nevertheless exert vital regulatory functions. They control transcription by modulating RNA polymerase passage and R-loop propagation, attracting transcription factors (TFs) or facilitating enhancer-promoter juxtaposition and supposedly participating in recombination, splicing, etc.…”

G-Quadruplexes: More Than Just a Kink in Microbial Genomes

“…The repertoire of cellular proteins binding G4s is both structurally and functionally diverse; it comprises a number of zinc-finger transcription factors (SP1, MAZ, PARP, CNBP), splicing factors (U2AF), proteins of the shelterin complex, RNA-binding proteins such as hnRNPs and RHAU, and RGG-box-containing multifunctional proteins, including nucleolin and FMRP [12][13][14]. Persistence of G4 structures can dysregulate the cellular activities they control and also compromise genomic integrity [15,16]. Helicases, including FANCJ, Pif1, DHX36 [17], BLM, and WRN, can unwind the G4s in eukaryotic genomes.…”