Long-range DNA interactions: inter-molecular G-quadruplexes and their potential biological relevance

Abstract

Guanine-rich DNA sequences are known to fold into secondary structures called G-quadruplexes (G4s), which can form from either individual DNA strands (intra-molecular) or multiple DNA strands (inter-molecular, iG4s). Intra-molecular G4s...

G‐Quadruplexes as Key Transcriptional Regulators in Neglected Trypanosomatid Parasites

“…These complex Figure 2. Representative examples of G4-ligands with reported anti-trypanosomal activity and selectivity: 2,9-bis[(substituted-aminomethyl)phenyl]-1,10phenanthroline, [18c] carbohydrate conjugated naphthalene diimide, [16a] dynamics between the formation of mutually exclusive G4s emphasize how the development of chemical probes that selectively target inter-molecular G4s [23] or RNA G4s [24] could be employed in the future to modulate parasite transcription in a rationally designed fashion.…”

“…It is becoming increasingly evident that inter‐molecular G4s can form in living organisms, linking distal DNA regions by G‐G base pairing [23] . For example, the recent discovery of a human protein that selectively recognises inter‐molecular versus intra‐molecular G4s [27] suggests that these distal G4s may form in humans.…”

Predicting the Three-dimensional Structure of the c-KITOncogene Promoter and the Dynamics of Strongly Coupled Guanine-Quadruplexes

“…As mentioned, in gene promoter regions G4s are usually coupled in clusters and this complex organization may lead to a welldefined three-dimensional of the individual G4s, which may strongly alter the interaction with their biological partners like helicases or with targeting molecules. [28][29][30] In a sense, and in analogy with protein or RNA classifications, while individual G4s may be assimilated to secondary structure elements, their interaction, especially when present on the same strand, could be defined as a tertiary arrangement. A perfect example of how complex the mutual arrangement of multiple neighboring G4s could be is represented by c-KIT gene promoter which features three G4s in close proximity, 31 namely WK1 and WK2 quadruplexes intertwined by the two tetrad WSP (see Figure 1), a system that was recently studied experimentally.…”

“…As mentioned, in gene promoter regions G4s are usually coupled in clusters and this complex organization may lead to a well-defined three-dimensional of the individual G4s, which may strongly alter the interaction with their biological partners like helicases or with targeting molecules. 28–30 In a sense, and in analogy with protein or RNA classifications, while individual G4s may be assimilated to secondary structure elements, their interaction, especially when present on the same strand, could be defined as a tertiary arrangement.…”

Predicting the Three-Dimensional Structure of the c-KIT Proto-Oncogene Promoter and the Dynamics of Its Strongly Coupled Guanine Quadruplexes

“…Long sequences containing two or three G4 units in the same strand have garnered significant attention. Pioneering work mainly focusing on the telomeric sequence has resulted in the development of two models for adjacent quadruplexes. , One model suggests that the G4 units are independent beads on a string, while the other suggests that they stack on top of each other, creating higher-order structures (G4–G4 cross-talk). , The human genome contains various G-rich sequences that have the potential to fold into multiple G4 motifs, including the promoters of hTERT, hRAS, and kRAS. − This complex organization may strongly alter the interaction with their biological partners such as helicases or targeting molecules. − By analogy to protein or RNA, while individual G4s can be considered to be secondary structure elements, the organization of adjacent G4s can be defined as a tertiary arrangement.…”