G ‐Quadruplexes ( G4s )

Abstract

Guanine‐rich regions of nucleic acids can fold into G‐quadruplex, a secondary structure formed by four strands of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). In the G‐quadruplex, guanines bind via Hoogsteen hydrogen bonds to yield the G‐quartet. Two or more G‐quartets stack on top of each other to form the G‐quadruplex, which can adopt different conformations, based both on the nature and orientation of the strands and on environmental factors such as cations. Both DNA and RNA G‐quadruplexes are found in biological systems: They have been computationally predicted and experimentally demonstrated by several methods in the genomes of several organisms, including humans, other eukaryotes, bacteria and viruses. G‐quadruplexes in the human cell genome are found in pivotal genomic regions, where they mainly act as regulatory elements. Several proteins process the G‐quadruplex. G‐quadruplex ligands that stabilise these structures are investigated against several diseases, as cancer and viral infections. In turn, G‐quadruplexes can themselves act as therapeutics. Key Concepts G‐quadruplexes are noncanonical nucleic acid structures that form in guanine‐rich sequences. G‐quadruplexes can form both in the DNA and RNA and are structurally extremely heterogeneous. Both computational and experimental methods have shown the presence of G‐quadruplexes in the genome of humans and other organisms, such as bacteria and viruses. G‐quadruplexes mainly function as epigenetic regulatory elements. G‐quadruplexes interact with a diverse array of cellular proteins, which induce, stabilise or destabilise them. Several methods have been developed to study the G‐quadruplex conformation in short oligonucleotides, longer sequences and whole genomes. Compounds that bind the G‐quadruplex are being studied as inhibitors of important human diseases such as cancer and infective diseases. G‐quadruplex‐folded aptamers have therapeutic potential.

Extreme jet ejections from the black hole X-ray binary V404 Cygni

“…V404 Cygni (aka GS 2023+338; hereafter referred to as V404 Cyg) is a well studied BHXB that has been in a lowluminosity quiescent state since its discovery with the Ginga satellite in 1989 (Makino 1989). This source has been observed to undergo a total of three outbursts prior to 2015; most recently in 1989 (Han & Hjellming 1992;Terada et al 1994;Oosterbroek et al 1997), and two prior to 1989 which were recorded on photographic plates (Richter 1989). V404 Cyg is known to display bright X-ray luminosities and high levels of multi-wavelength variability, both in outburst and quiescence (Tanaka & Lewin 1995;Hynes et al 2002;Hjellming & Han 1989;Kitamoto et al 1989).…”

Tracking the variable jets of V404 Cygni during its 2015 outburst

“…V404 Cyg underwent three known outbursts prior to 2015: 1938 (when the optical counterpart was observed and originally identified as Nova Cygni; Wagner et al 1989), 1956 (as discovered on photographic plates ;Richter 1989), and 1989 (when the transient X-ray counterpart was first identified by the Ginga satellite; Makino 1989). The 1989 outburst was monitored at multiple frequencies, including X-ray, optical, and radio frequencies (Han & Hjellming 1992).…”