DNA hypomethylation leads to elevated mutation rates

Richard Z. Chen, Ulf Pettersson, Caroline Beard, Laurie Jackson-Grusby and Rudolf Jaenisch ()
Additional contact information
Richard Z. Chen: Whitehead Institute for Biomedical Research
Ulf Pettersson: Whitehead Institute for Biomedical Research
Caroline Beard: Whitehead Institute for Biomedical Research
Laurie Jackson-Grusby: Whitehead Institute for Biomedical Research
Rudolf Jaenisch: Whitehead Institute for Biomedical Research

Nature, 1998, vol. 395, issue 6697, 89-93

Abstract: Abstract Genome-wide demethylation has been suggested to be a step in carcinogenesis1. Evidence for this notion comes from the frequently observed global DNA hypomethylation in tumour cells2, and from a recent study suggesting that defects in DNA methylation might contribute to the genomic instability of some colorectal tumour cell lines3. DNA hypomethylation has also been associated with abnormal chromosomal structures, as observed in cells from patients with ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome4,5 and in cells treated with the demethylating agent 5-azadeoxycytidine6. Here we report that murine embryonic stem cells nullizygous for the major DNA methyltransferase (Dnmt1) gene exhibited significantly elevated mutation rates at both the endogenous hypoxanthine phosphoribosyltransferase (Hprt) gene and an integrated viral thymidine kinase (tk) transgene. Gene deletions were the predominant mutations at both loci. The major cause of the observed tk deletions was either mitotic recombination or chromosomal loss accompanied by duplication of the remaining chromosome. Our results imply an important role for mammalian DNA methylation in maintaining genome stability.

Date: 1998
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/25779 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:395:y:1998:i:6697:d:10.1038_25779

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/25779

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().