History of DNA Helicases

Abstract

Since the discovery of the DNA double helix, there has been a fascination in understanding the molecular mechanisms and cellular processes that account for: (i) the transmission of genetic information from one generation to the next and (ii) the remarkable stability of the genome. Nucleic acid biologists have endeavored to unravel the mysteries of DNA not only to understand the processes of DNA replication, repair, recombination, and transcription but to also characterize the underlying basis of genetic diseases characterized by chromosomal instability. Perhaps unexpectedly at first, DNA helicases have arisen as a key class of enzymes to study in this latter capacity. From the first discovery of ATP-dependent DNA unwinding enzymes in the mid 1970’s to the burgeoning of helicase-dependent pathways found to be prevalent in all kingdoms of life, the story of scientific discovery in helicase research is rich and informative. Over four decades after their discovery, we take this opportunity to provide a history of DNA helicases. No doubt, many chapters are left to be written. Nonetheless, at this juncture we are privileged to share our perspective on the DNA helicase field – where it has been, its current state, and where it is headed.

DNA folds threaten genetic stability and can be leveraged for chemotherapy

“…oncogene expression modulation for promoter G4s; telomere stability for telomeric G4s). 190,192,269 209,212,214,215 Name Family 216,217 And yet, G4 formation is intimately linked to all DNA transactions, favoured by the transient formation of ssDNA during DNA-replication and DNA-to-RNA transcription, when the B-helix is split apart and the single strands are subjected to negative supercoiling, in which helical tension is theorised to cause the DNA to curl like a twisted string. Whilst transactions induce their formation, G4s can physically impede these two processes, stopping or stalling the advancing polymerase, triggering DNA damage and activating DDR mechanisms.…”

Using in silico modelling and FRET-based assays in the discovery of novel FDA-approved drugs as inhibitors of MERS-CoV helicase

“…Helicases have been identified in the genomes of all three life kingdoms and in the genomes of many viruses [10]. An estimated 31 DNA helicases and 64 RNA helicases are encoded in the human genome [11]. The unwinding of the DNA through helicase activity is a central step in many cellular processes including replication, recombination, and DNA repair [12].…”

Effects of Conserved Wedge Domain Residues on DNA Binding Activity of Deinococcus radiodurans RecG Helicase

“…ATP-dependent duplex DNA unwinding enzymes, termed DNA helicases, are prevalent in all kingdoms of life and play important roles in the processes of DNA replication, repair, recombination, etc. ( Brosh and Matson, 2020 ). The human genome encodes for 31 nonredundant DNA helicases ( Umate et al, 2011 ).…”

“…Given their fundamental roles in DNA metabolism, mutations in some of these genes are associated with certain human diseases characterized by premature aging and cancer, including Xeroderma Pigmentosum, Cockayne Syndrome, and Werner Syndrome ( Uchiumi et al, 2015 ). Since DNA helicase was first discovered in the model bacterium Escherichia coli ( Brosh and Matson, 2020 ), the E. coli helicases have been intensively studied, and their function has been compared to that of counterparts identified in different organisms. In E. coli , HR initiation follows the RecBCD pathway.…”