Ultrasensitive colorimetric sensing of DNA methyltransferase activity based on signal amplification by modulating cascade reaction

DNA methylation is a critical genomic epigenetic modification, and abnormal levels of it can lead to various cancers and genetic disorders. Therefore, the detection of DNA methyltransferase is of great importance for related disease diagnosis. This study reports a signal amplification method for detecting the activity of adenine methylation methyltransferase (Dam MTase). The ultrasensitive colorimetric sensor functions by modulating a cascade reaction that involves the catalytic reaction of platinum nanoparticles (PtNPs) and the release of Ag + from silver nanoparticle (AgNP) tags. Magnetic beads (MBs) and AgNPs are preconnected through DNA hybridization. The DNA linker can be methylated by Dam MTase and thereby cleaved by methylation-sensitive endonuclease Dpn I. The MBs separated from AgNPs cannot release Ag + to inactivate PtNPs. With original superior catalysis ability of PtNPs, Dam MTase can be monitored by catalyzing the generation of signal molecules. This biosensor exhibits a linear range of 0.2–2 U/mL Dam MTase activity with a detection limit of 0.04 U/mL. Additionally, it proves effective for real sample analysis and methylation inhibitor screening.