N-6-Methyl-2-deoxyadenosine

N-6-Methyl-2-deoxyadenosine (m6dA) is an adenine nucleoside analogue. N-6-Methyl-2-deoxyadenosine targets nuclear processes and DNA replication machineries including WER, SATB1, TFAM, Jumu, SSBP1, DNA polymerase η and phage polymerase Gp90 exo⁻. N-6-Methyl-2-deoxyadenosine acts as a multifunctional epigenetic regulator that modulates transcription, DNA damage response, cell cycle, transposon silencing, stress adaptation, epigenetic crosstalk, and nucleosome organization in both prokaryotes and eukaryotes. N-6-Methyl-2-deoxyadenosine regulates mitochondrial epigenetic inheritance and is required for fear extinction memory in mice. N-6-Methyl-2-deoxyadenosine exhibits dysregulated levels in cancers. N-6-Methyl-2-deoxyadenosine can be used for the research of glioblastoma, triple negative breast cancer, and conditioned fear (fear extinction impairment)^[1][2]. In Vitro:N-6-Methyl-2-deoxyadenosine causes site-specific transcriptional pausing by Saccharomyces cerevisiae RNA polymerase II^[1].
N-6-Methyl-2-deoxyadenosine inhibits DNA replication by human DNA polymerase-η in vitro^[1].
N-6-Methyl-2-deoxyadenosine enhances the DNA-binding affinity of human mitochondrial SSBP1, reduces TFAM-mediated mtDNA transcription, and can be catalyzed and deposited onto mammalian mitochondrial DNA by human METTL4 in vitro^[1].
N-6-Methyl-2-deoxyadenosine reduces the binding affinity of Arabidopsis thaliana transcription factor WER to its target DNA motifs in vitro^[1].
N-6-Methyl-2-deoxyadenosine slightly increases the binding affinity of Drosophila melanogaster transcription factor Jumu to DNA in vitro^[1].
N-6-Methyl-2-deoxyadenosine inhibits DNA replication by Pseudomonas aeruginosa phage PaP1 DNA polymerase Gp90 exo^{− [1]}.
N-6-Methyl-2-deoxyadenosine (20 mM; 7 h) was measured in mouse primary cortical neurons (7 days in vitro) treated with KCl, which exhibited a significant increase in global m6dA levels^[2]. In Vivo:N-6-Methyl-2-deoxyadenosine drives extinction-induced Bdnf exon IV expression in the mouse ILPFC and is required for the formation of fear extinction memory, with median freezing in extinction-trained N6amt1 knockdown mice reaching 49.68% compared to 10.57% in scrambled controls^[2].