Previous studies have shown that DNA methyltransferase (Dnmt) 1 is required for 
maintenance of bulk DNA methylation and is essential for mouse development. 
However, somatic disruption of DNMT1 in the human cancer cell line HCT116 was 
not lethal and caused only minor decreases in methylation. Here, we report the 
identification of a truncated DNMT1 protein, which was generated by the 
disruption of DNMT1 in HCT116 cells. The truncated protein, which had parts of 
the regulatory N-terminal domain deleted but preserved the catalytic C-terminal 
domain, was present at different levels in all DNMT1 single-knockout and 
DNMT1/DNMT3b double-knockout cell lines tested and retained hemimethylase 
activity. DNMT1 RNAi resulted in decreased cell viability in WT and knockout 
cells and further loss of DNA methylation in DNMT1 knockout cells. Furthermore, 
we observed a delay in methylation after replication and an increase in 
hemimethylation of specific CpG sites in cells expressing the truncated protein. 
Remethylation studies after drug-induced hypomethylation suggest a putative role 
of DNMT1 in the de novo methylation of a subtelomeric repeat, D4Z4, which is 
lost in cells lacking full-length DNMT1. Our data suggest that DNMT1 might be 
essential for maintenance of DNA methylation, proliferation, and survival of 
cancer cells.