Document Detail


Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells.
MedLine Citation:
PMID:  17322882     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Studies have shown that DNA (cytosine-5-)-methyltransferase 1 (DNMT1) is the principal enzyme responsible for maintaining CpG methylation and is required for embryonic development and survival of somatic cells in mice. The role of DNMT1 in human cancer cells, however, remains highly controversial. Using homologous recombination, here we have generated a DNMT1 conditional allele in the human colorectal carcinoma cell line HCT116 in which several exons encoding the catalytic domain are flanked by loxP sites. Cre recombinase-mediated disruption of this allele results in hemimethylation of approximately 20% of CpG-CpG dyads in the genome, coupled with activation of the G2/M checkpoint, leading to arrest in the G2 phase of the cell cycle. Although cells gradually escape from this arrest, they show severe mitotic defects and undergo cell death either during mitosis or after arresting in a tetraploid G1 state. Our results thus show that DNMT1 is required for faithfully maintaining DNA methylation patterns in human cancer cells and is essential for their proliferation and survival.
Authors:
Taiping Chen; Sarah Hevi; Frédérique Gay; Naomi Tsujimoto; Timothy He; Bailin Zhang; Yoshihide Ueda; En Li
Publication Detail:
Type:  Journal Article     Date:  2007-02-18
Journal Detail:
Title:  Nature genetics     Volume:  39     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-27     Completed Date:  2007-06-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  391-6     Citation Subset:  IM    
Affiliation:
Epigenetics Program, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Alleles
Cell Proliferation
Cell Survival
Colorectal Neoplasms / genetics*,  metabolism
DNA (Cytosine-5-)-Methyltransferase / genetics*,  physiology
DNA Methylation
HCT116 Cells
Humans
Mitosis*
Models, Biological
Models, Genetic
Chemical
Reg. No./Substance:
EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA (cytosine-5-)-methyltransferase 1
Comments/Corrections
Comment In:
Nat Genet. 2007 Mar;39(3):289-90   [PMID:  17325677 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase ...
Next Document:  Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus cal...