Structure and Function of Multimeric G-quadruplexes

Abstract

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

Diversity of Parallel Guanine Quadruplexes Induced by Guanine Substitutions

“…Any addition of terminal overhangs leads to an increase in PAGE migration speed, but the migration speed cannot be simply attributed to the molecularity of the complex. There is still a significant difference in migration between Q and T30695 suggesting that the Q might form even higher than bimolecular species, such as tetramolecular etc, although the 5′-5′ (head-to-head) end stacking seems to be preferred over 3′-3′ (tail-to-tail) or 5′-3′ (head-to-tail) [ 25 , 33 ]. In the case of 5′-3′ stacking or the simultaneous presence of 5′-5′ and 3′-3′ end stacking even higher associates would be expected, but we did not observe any such species.…”

“…(ii) The molecularity, i.e., presence of multiple strands in the quadruplex, possibly a result of various modes of interaction, which do not lead to the same change in migration. We will further refer the hydrogen bonded interlocked G4 as bimolecular (second mode in [ 25 ]), compared to dimer, caused by 5′-5′ end stacking (first mode in [ 25 ]). (iii) The presence of terminal tetrads exposed to the solvent, which significantly slows down the migration.…”

“…Moreover, parallel quadruplexes tend to form multimers [ 24 ] even in cases where the primary sequence allows the formation of a monomolecular quadruplex. The multimerisation might result from several different modes [ 24 , 25 ], including terminal tetrad stacking with a strong 5′-5′ end stacking preference [ 26 ], reported also for tetramolecular parallel quadruplexes [ 27 ]. No interstrand guanine bonding is present here.…”

Cockayne Syndrome B protein selectively interacts and resolves intermolecular DNA G-quadruplex structures

“…We observed that CSB is able to resolve only a small sub-population of G4s formed by rDNA. Further analysis revealed that CSB has an ATP-independent G4-resolvase activity that is limited to intermolecular G4s 20 that can be formed by rDNA sequences, whilst being inactive towards intramolecular G4s formed by both rDNA and non-rDNA sequences. We further observed that CSB can bind with astonishing picomolar affinity intermolecular rDNA G4s, whilst displaying negligible binding towards unimolecular G4s formed by the same rDNA sequences.…”

In-depth Bioinformatic Analyses of Human SARS-CoV-2, SARS-CoV, MERS-CoV, and OtherNidoviralesSuggest Important Roles of Noncanonical Nucleic Acid Structures in Their Lifecycles

“…G-quadruplexes are secondary nucleic acid structures formed in guanine-rich strands (Burge et al, 2006;Vorlíčková et al, 2012;Kolesnikova and Curtis, 2019). These have been detected in various This is a provisional file, not the final typeset article genomes, but most extensively they have been described in human genomes (Chambers et al, 2015;Bedrat et al, 2016;Hänsel-Hertsch et al, 2016).…”