摘要：SummaryDNA methyl transferase-1 or DNMT1 maintains DNA methylation in the genome and is important for regulating gene expression in cells. Aberrant changes in DNMT1 activity and DNA methylation are commonly observed in cancers and many other diseases. Recently, a number of long intergenic non-protein-coding RNAs or lincRNAs have been shown to play a role in regulating DNMT1 activity.CCDC26is a nuclear lincRNA that is frequently mutated in cancers and is a hotbed for disease-associated single nucleotide changes. However, the functional mechanism ofCCDC26is not understood. Here, we show that this lincRNA is concentrated on the nuclear periphery. Strikingly, in the absence ofCCDC26lincRNA, DNMT1 is mis-located in the cytoplasm, and the genomic DNA is significantly hypomethylated. This is accompanied by double-stranded DNA breaks and increased cell death. These results point to a previously unrecognized mechanism of lincRNA-mediated subcellular localization of DNMT1 and regulation of DNA methylation.Graphical abstractDisplay OmittedHighlights•LincRNA CCDC26 influences cellular localization of the enzyme DNMT1•In the absence of CCDC26, the genomic DNA is significantly hypomethylated•Removal of CCDC26 leads to double-stranded DNA breaks and increased cell deathMolecular Biology; Cell Biology
