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.
Highlights
Section on DNA Helicases, Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Researchers investigated the activity of select helicases on nucleic acid structures that arise in specific pathways of cellular DNA metabolism. One such substrate is the Holliday Junction (HJ), a branched DNA molecule with four double-stranded arms that represents a key intermediate of genetic recombination and double-strand break repair that occurs during the S/G2 phases of the cell cycle
It was during this period that hereditary disorders characterized by DNA repair defects and/or chromosomal instability, a predisposition to cancer, and in certain cases, accelerated aging phenotypes were linked to mutations in helicase genes
Summary
The discovery of proteins capable of ATP-dependent enzymatic unwinding of duplex DNA was first reported in 1976 by Hoffmann-Berling and colleagues at the University of Heidelberg [1,2]. Linn described E. coli RecBC as an ATP-dependent unwinding enzyme in which catalytic duplex strand separation was detectable (under conditions where the nuclease is suppressed by a DNA binding protein), leading them to hypothesize that “the major contribution of RecBC enzyme to recombination would be the unwinding of DNA” [3] From both biochemical and genetic viewpoints, the discovery of DNA helicases immediately provoked speculation regarding their mechanisms and biological roles. DNA helicases were isolated from bovine mitochondria [12] and pea were an estimated 95 helicases or putative helicases encoded by the human genome; 31 DNA chloroplasts [13], indicating their ubiquitous presence. Molecular and cellular studies have elucidated the functional aspects of numerous DNA helicases in ago, Narendra and Renu Tuteja provided a historical account of prokaryotic and eukaryotic DNA various pathways of nucleic acid metabolism. Prediction of human DNA and RNA helicases [11]
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