A real-time biochemical assay for quantitative analyses of APOBEC-catalyzed DNA deamination

bioRxiv [Preprint]. 2024 May 12:2024.05.11.593688. doi: 10.1101/2024.05.11.593688.

Abstract

Over the past decade, the connection between APOBEC3 cytosine deaminases and cancer mutagenesis has become increasingly apparent. This growing awareness has created a need for biochemical tools that can be used to identify and characterize potential inhibitors of this enzyme family. In response to this challenge, we have developed a Real-time APOBEC3-mediated DNA Deamination (RADD) assay. This assay offers a single-step set-up and real-time fluorescent read-out, and it is capable of providing insights into enzyme kinetics and also offering a high-sensitivity and easily scalable method for identifying APOBEC3 inhibitors. This assay serves as a crucial addition to the existing APOBEC3 biochemical and cellular toolkit and possesses the versatility to be readily adapted into a high-throughput format for inhibitor discovery.

Keywords: APOBEC3; biotechnology; cancer; cytidine deaminase; fluorescence resonance energy transfer (FRET); high-throughput screening (HTS); mutagenesis; protein-DNA interaction; real-time assay; somatic mutations.

Publication types

  • Preprint