The Dnmt1 enzyme is a member of the C5-methyltransferase family responsible for repairing cytosines in double-stranded DNA (dsDNA). This enzyme uses a nucleophilic attack mechanism and is the most abundantly found mammalian DNA methyltransferase. It primarily acts upon CpG residues and prefers hemimethylated residues, but can also methylating unmethylated DNA. The cell relies upon Dnmt1 as its key methylation maintenance enzyme both for DNA replication and repair as well as for de novo methylation during somatic cell development and differentiation. In cell division, it is required for epigenetic inheritance because it complexes with S-phase DNA replication sites to faithfully maintain the original methylation pattern into the newly made strand. To maintain the DNA methylated state of the DNA independently of replication, Dnmt1 also regularly cycles through states of complex formation and localization. It has the following expression pattern: associated with chromatin during G2 and M phases, reduced to undetectable levels during G0, and dramatically induced and upregulated upon the cell’s S-phase entry.
Immunohistochemistry-Paraffin: DNMT1 Antibody (60B1220.1) [NB100-56519] - IHC-P validation of DNMT1 antibody (clone 60B1220.1) on formalin fixed and paraffin embedded tissue section of human hepatocellular carcinoma at 1:50 dilution.
Rhee's group at the HHMI at Johns Hopkins published exciting results in Nature demonstrating that both Dnmt1 and Dnmt3b cooperatively control DNA methylation and gene silencing in colorectal cancer cells, and that this epigenetic silencing is essential for neoplastic growth (1). Their results relied upon immunoblotting experiments with the Dnmt1 antibody. Robert et al from MethylGene in Canada used the Dnmt1 antibody to map aberrant CpG island methylation and the effects of Dnmt pharmacologic inhibitors (both genetic and pharmacological) (2). Their Nature Genetics paper shares their attempts to better understand the role of Dnmt alleles and isotypes in the progression of bladder and colon cancers. The Dnmt1 antibody allowed Leu et al from the OSU Cancer Center to investigate the role of epigenetic silencing on downstream targets for the estrogen receptor (ER) (3). Their novel results suggest that epigenetic regulation has a big function in modulating ERalpha target genes, and they discuss the implications this has for breast cancer genome-targeted therapy. Detailed immunohistochemical studies with the Dnmt1 antibody were performed by Lai's group to provide better insight into the molecular dynamics of silencing during B-cell activation and differentiation (4). A novel qualitative proteomic analysis with the Dnmt1 antibody was employed by Grau’s group for their studies on bladder cancer aggressiveness (5). This group started with a pool of 289 differentially expressed proteins which they were able to focus down to a smaller subset for study. Their endpoint studies focused on the ubiquitination protein Cul3, and they determined that the Cul3-dependent downregulation of certain cytoskeletal proteins (ezrin, filamin, and caveolin) conferred greater invasive and proliferative properties to those cells.
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