DNA Tile Self‐Assembly Guided by Base Excision Repair Enzymes. (14th July 2022)

• Record Type: Journal Article
• Authors: Farag, Nada; Ercolani, Gianfranco; Del Grosso, Erica; Ricci, Francesco
• Is Part Of: Angewandte Chemie. Volume 134:Number 34(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-14
• Subjects: DNA Nanotechnology -- DNA Repair Enzymes -- DNA Structures -- DNA Tiles -- Self-Assembly; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202208367
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: We demonstrate here the use of DNA repair enzymes to control the assembly of DNA‐based structures. To do so, we employed uracil‐DNA glycosylase (UDG) and formamidopyrimidine DNA glycosylase (Fpg), two enzymes involved in the base excision repair (BER) pathway. We designed two responsive nucleic acid modules containing mutated bases (deoxyuridine or 8‐oxo‐7, 8‐dihydroguanine recognized by UDG and Fpg, respectively) that, upon the enzyme repair activity, release a nucleic acid strand that induces the self‐assembly of DNA tiles into tubular structures. The approach is programmable, specific and orthogonal and the two responsive modules can be used in the same solution without crosstalk. This allows to assemble structures formed by two different tiles in which the tile distribution can be accurately predicted as a function of the relative activity of each enzyme. Finally, we show that BER‐enzyme inhibitors can also be used to control DNA‐tile assembly in a specific and concentration‐dependent manner. Abstract : The assembly of DNA polymeric tubular structures guided by the activity of two base excision repair (BER) enzymes: uracil DNA glycosylase (UDG) and formamidopyrimidine DNA glycosylase (Fpg) is demonstrated. Orthogonal DNA tiles were designed that can be specifically activated by each enzyme and assembled into DNA co‐polymers with highly predictable tile distribution.