G4-interacting proteins endangering genomic stability at G4 DNA-forming sites

Abstract

In guanine-rich DNA strands, base-base interactions among guanines allow the conformational shift from the B-form DNA to the non-canonical quadruplex or G4 structure. The functional significance of G4 DNA in vivo is largely dependent on the interaction with protein factors, many of which contain the arginine–glycine–glycine or RGG repeat and other consensus G4-binding motifs. These G4-interacting proteins can significantly modulate the effect of G4 DNA structure on genome maintenance, either preventing or aggravating G4-assoicated genome instability. While the role of helicases in resolving G4 DNA structure has been extensively discussed, identification and characterization of protein factors contributing to elevation in G4-associated genome instability has been relatively sparse. In this minireview, we will particularly highlight recent discoveries regarding how interaction between certain G4-binding proteins and G4 DNA could exacerbate genome instability potentiated by G4 DNA-forming sequences.