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Since its inception in 1962, the Nucleic Acids Gordon Conference has been a premier venue for the dissemination of exciting and transformative discoveries concerning the structure and function of DNA and RNA and the complex mechanisms underlying DNA/RNA synthesis, processing, modification, and repair and the regulation of nucleic acid transactions at all stages of gene expression. The 2019 Nucleic Acids GRC continues the tradition of featuring cutting-edge basic research, emerging concepts, and novel technologies in an informal setting conducive to cross-disciplinary discussions and exchange of ideas. In addition to covering the areas cited above, the 2019 conference will highlight in a new thematic session the diverse and important roles that nucleic acids and nucleic acid sensors play in innate and acquired immunity. New DNA and RNA modifications are being discovered apace and the 2019 conference will explore their mechanisms of synthesis and biological impact. Insights from structural biology, and especially cryo-EM, into the operation of the large and complex machines that act on DNA and RNA will figure prominently at this GRC. As an added attraction for young scientists, this meeting will feature an associated 2019 Nucleic Acids Gordon Research Seminar (GRS), held on June 1-2, just before the main GRC. The GRS is a valuable forum for students and postdocs to present their research and share their ideas about science and career.