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NOS2 promotes passive DNA demethylation and LINE-1 expression. (Left) Under normal physiological conditions, DNMT1 methylates the nascent DNA strand during replication and LINE-1 retrotransposons are silenced by promoter CpG methylation. (Right) NOS2 expression results in sustained p38-MAPK activation, which leads to DNMT1 protein degradation. Replication in the absence of DNMT1 activity results in passive DNA demethylation, LINE-1 expression, and genomic instability.
