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

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.