Natural and Synthetic Strategies for DNA Maintenance and Recording

Abstract

As the sole guardian of the necessary knowledge for the creation of life (as we know), the genomic DNA is carefully protected by extremely diligent repair pathways. Highlighting the importance of these repair processes are thousands of genetic diseases that are caused by just a single nucleotide mutation (in genomes that are made of billions of nucleotides). On the other hand, adaptation, which is at the very core of the concept of life, relies on the ability of living cells to incorporate value-added information to the genome. Thus, mutations (which provide substrates for adaptation) are also essential and permitted to occur naturally. The dynamic interplay between the DNA damaging/modifying agents/enzymes and the DNA repair machinery determines the editing outcome of the book of life. Therefore, genomic DNA can be considered as a biological hard drive in living cells, where information can be added, saved or erased by two competing processes. The continued quest to better understand the mechanisms underlying cellular DNA repair processes on one hand, and the technological advances that allow us to dynamically write arbitrary information into the genome, on the other hand, are the keys to understanding and controlling the flow of information into this biological hard drive. Here, I first present our current outlook to the genome maintenance and DNA repair processes. I then discuss various DNA writing strategies. In addition, I will outline how the interplay between DNA repair machinery and these technologies can be leveraged to both dynamically and precisely control the flow of information into the genomic DNA, as well as better understand the underlying mechanisms of DNA repair pathways. The synergic advances in these areas could ultimately let us gain control over the book of life, with applications ranging from the study of human biology and diseases to programming cellular phenotypes.