A mutant DNMT1 enhances tumorigenicity with focal hypermethylation and global hypomethylation

ABSTRACT: Site-specific hypermethylation of tumor suppressor genes accompanied by genome-wide hypomethylation are epigenetic hallmarks of malignancy. However, molecular mechanisms that drive these linked changes in DNA methylation remain obscure. DNA methyltransferase 1 (DNMT1), the principle enzyme responsible for maintaining methylation patterns is commonly dysregulated in tumors. Replication foci targeting sequence (RFTS) is an N-terminal domain of DNMT1 that inhibits DNA-binding and catalytic activity, suggesting that RFTS deletion would result in gain of DNMT1 function. However, earlier data suggested that RFTS is required for DNMT1 activity. Here, we determined cellular consequences of RFTS deletion from DNMT1 in immortalized human bronchial epithelial cells. Compared to full-length DNMT1, ect

ORGANISM(S): Homo sapiens

SUBMITTER: Charles Brenner 

PROVIDER: E-GEOD-57829 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress