title: Unintended Consequences of Expanding the Genetic Alphabet.
abstract: The base pair d5SICS·dNaM was recently reported to incorporate and replicate in the DNA of a modified strain of Escherichia coli, thus making the world's first stable semisynthetic organism. This newly expanded genetic alphabet may allow organisms to store considerably more information in order to translate proteins with unprecedented enzymatic activities. Importantly, however, there is currently no knowledge of the photochemical properties of d5SICS or dNaM-properties that are central to the chemical integrity of cellular DNA. In this contribution, it is shown that excitation of d5SICS or dNaM with near-visible light leads to efficient trapping of population in the nucleoside's excited triplet state in high yield. Photoactivation of these long-lived, reactive states is shown to photosensitize cells, leading to the generation of reactive oxygen species and to a marked decrease in cell proliferation, thus warning scientists of the potential phototoxic side effects of expanding the genetic alphabet.
authors: Department of Chemistry, Case Western Reserve University , Cleveland, Ohio 44106, United States.
authors: Marvin
authors: M
authors: Pollum
authors: Department of Chemistry, Case Western Reserve University , Cleveland, Ohio 44106, United States.
authors: Brennan
authors: B
authors: Ashwood
authors: Department of Chemistry, Columbia University , New York, New York 10027, United States.
authors: Steffen
authors: S
authors: Jockusch
authors: Department of Dermatology, Case Western Reserve School of Medicine , Cleveland, Ohio 44106, United States.
authors: Minh
authors: M
authors: Lam
authors: Department of Chemistry, Case Western Reserve University , Cleveland, Ohio 44106, United States.
authors: Carlos E
authors: CE
authors: Crespo-Hernández
mesh_terms: D020029:Base Pairing; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics*; D005815:Genetic Code; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D004247:DNA