Localization and discrimination of GG mismatch in duplex DNA by synthetic ligand-enhanced protein nanopore analysis.

Autor:	Lyu W; Department of Chemistry and Chemical Engineering, Guangzhou Key Laboratory for Environmentally Functional Materials and Technology, Guangzhou University, 230 Wai Huan Xi Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China.; Department of Physics, RWTH Aachen University, Templergraben 55, 52062 Aachen, Germany., Zhu J; Department of Chemistry and Chemical Engineering, Guangzhou Key Laboratory for Environmentally Functional Materials and Technology, Guangzhou University, 230 Wai Huan Xi Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China., Huang X; Department of Chemistry and Chemical Engineering, Guangzhou Key Laboratory for Environmentally Functional Materials and Technology, Guangzhou University, 230 Wai Huan Xi Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China., Chinappi M; Univ Roma Tor Vergata, Dept Ind Engn, Via Politecn 1, I-00133 Rome, Italy., Garoli D; Istituto Italiano di Tecnologia, Via Morego 30, 16136 Genova, Italy.; Dipartimento di Scienze e Metodi dell'Ingegneria, Università di Modena e Reggio Emilia, via Amendola 2, 42122 Reggio Emilia, Italy., Gui C; Department of Chemistry and Chemical Engineering, Guangzhou Key Laboratory for Environmentally Functional Materials and Technology, Guangzhou University, 230 Wai Huan Xi Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China., Yang T; Department of Chemistry and Chemical Engineering, Guangzhou Key Laboratory for Environmentally Functional Materials and Technology, Guangzhou University, 230 Wai Huan Xi Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China., Wang J; Department of Chemistry and Chemical Engineering, Guangzhou Key Laboratory for Environmentally Functional Materials and Technology, Guangzhou University, 230 Wai Huan Xi Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Nov 11; Vol. 52 (20), pp. 12191-12200.
DOI:	10.1093/nar/gkae884
Abstrakt:	Mismatched base pairs in DNA are the basis of single-nucleotide polymorphism, one of the major issues in genetic diseases. However, the changes of physical and chemical properties of DNA caused by single-site mismatches are often influenced by the sequence and the structural flexibility of the whole duplex, resulting in a challenge of direct detection of the types and location of mismatches sensitively. In this work, we proposed a synthetic ligand-enhanced protein nanopore analysis of GG mismatch on DNA fragment, inspired by in silico investigation of the specific binding of naphthyridine dimer (ND) on GG mismatch. We demonstrated that both the importing and unzipping processes of the ligand-bound DNA duplex can be efficiently slowed down in α-hemolysin nanopore. This ligand-binding induced slow-down effect of DNA in nanopore is also sensitive to the relative location of the mismatch on DNA duplex. Especially, the GG mismatch close to the end of a DNA fragment, which is hard to be detected by either routine nanopore analysis or tedious nanopore sequencing, can be well differentiated by our ND-enhanced nanopore experiment. These findings provide a promising strategy to localize and discriminate base mismatches in duplex form directly at the single-molecule level. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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