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Updated: May 21, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Mutations in DNA methyltransferase (DNMT3A) observed in acute myeloid leukemia patients disrupt processive
Celeste Holz-Schietinger1, Doug M Matje, Norbert O Reich
1Interdepartmental Program in Biomolecular Science and Engineering, University of California, Santa Barbara, California 93106-9510, USA.
Abstract:
DNA methylation is a key regulator of gene expression and changes in DNA methylation occur early in tumorigenesis. Mutations in the de novo DNA methyltransferase gene, DNMT3A, frequently occur in adult acute myeloid leukemia patients with poor prognoses. Most of the mutations occur within the dimer or tetramer interface, including Arg-882. We have identified that the most prevalent mutation, R882H, and three additional mutants along the tetramer interface disrupt tetramerization. The processive methylation of multiple CpG sites is disrupted when tetramerization is eliminated. Our results provide a possible mechanism that accounts for how DNMT3A mutations may contribute to oncogenesis and its progression.
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