G4 Biology and Scope for Potential Therapeutic Intervention against Multiple Disease Adversaries

DNA - the repository of genetic information harbours sequences rich in Guanine that adopt non-B form four-stranded DNA secondary structures termed as G-quadruplexes (G4s). Such non-canonical structures tend to impede the progression of routine replisome and are implicated to have crucial roles in replication, transcription and epigenetic regulation while also ensuring genomic stability. It is now fully established that G4s are enzymatically unfolded by helicases, thus, preventing transient yet apparent impediments to the vital replisome progression. This unfolding of G-quadruplex ensures genetic and epigenetic stability. Given the importance of G4 biology for multiple human parasites such as, Mycobacterium tuberculosis, research efforts probing parasitic G4 biology is gaining momentum with the hope to enable therapeutic intervention. We herein shed light on G4s, conditions that lead to their formation and the mechanisms employed by cells to cause their unfolding. Towards the end, potential drug discovery avenues that arise from targeting parasitic helicases and G4 biology are summarized.