Document Detail


DNMTs are required for delayed genome instability caused by radiation.
MedLine Citation:
PMID:  22722331     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ability of ionizing radiation to initiate genomic instability has been harnessed in the clinic where the localized delivery of controlled doses of radiation is used to induce cell death in tumor cells. Though very effective as a therapy, tumor relapse can occur in vivo and its appearance has been attributed to the radio-resistance of cells with stem cell-like features. The molecular mechanisms underlying these phenomena are unclear but there is evidence suggesting an inverse correlation between radiation-induced genomic instability and global hypomethylation. To further investigate the relationship between DNA hypomethylation, radiosensitivity and genomic stability in stem-like cells we have studied mouse embryonic stem cells containing differing levels of DNA methylation due to the presence or absence of DNA methyltransferases. Unexpectedly, we found that global levels of methylation do not determine radiosensitivity. In particular, radiation-induced delayed genomic instability was observed at the Hprt gene locus only in wild-type cells. Furthermore, absence of Dnmt1 resulted in a 10-fold increase in de novo Hprt mutation rate, which was unaltered by radiation. Our data indicate that functional DNMTs are required for radiation-induced genomic instability, and that individual DNMTs play distinct roles in genome stability. We propose that DNMTS may contribute to the acquirement of radio-resistance in stem-like cells.
Authors:
Christine A Armstrong; George D Jones; Rhona Anderson; Pooja Iyer; Deepan Narayanan; Jatinderpal Sandhu; Rajinder Singh; Christopher J Talbot; Cristina Tufarelli
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-22
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  7     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-28     Completed Date:  2013-01-14     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  892-902     Citation Subset:  IM    
Affiliation:
Department of Genetics, University of Leicester, Leicester, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
DNA (Cytosine-5-)-Methyltransferase / genetics,  physiology*
DNA Methylation / genetics,  radiation effects
Embryonic Stem Cells / radiation effects
Genomic Instability / genetics,  radiation effects*
Hypoxanthine Phosphoribosyltransferase / genetics
Mice
Mutation Rate
Radiation Tolerance*
Grant Support
ID/Acronym/Agency:
//Biotechnology and Biological Sciences Research Council
Chemical
Reg. No./Substance:
EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA (cytosine-5-)-methyltransferase 1; EC 2.4.2.8/Hypoxanthine Phosphoribosyltransferase
Comments/Corrections

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


Previous Document:  New classes of carborane-appended 5-thio-d-glucopyranose derivatives.
Next Document:  Highly controlled synthesis of nanometric gold particles by citrate reduction using the short mixing...