Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Search research articles

Related Experiment Videos

DNA hypomethylation leads to elevated mutation rates

R Z Chen¹, U Pettersson, C Beard

¹Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.

|September 17, 1998

Summary

Global DNA hypomethylation, a hallmark of cancer, is linked to genomic instability. Loss of the DNA methyltransferase (Dnmt1) gene in mice dramatically increases mutation rates, highlighting DNA methylation's role in genome stability.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

[The optimal examination duration for the detection of epileptiform discharge in outpatient video-electroencephalography].

Zhonghua yi xue za zhi·2023

Same author

[Effect and safety of endobronchial placement of vaseline gauze in the treatment of patients with bronchial fistula].

Zhonghua yi xue za zhi·2022

Same author

[Preoperative serum creatinine as an independent prognostic biomarker in patients with early-stage cervical adenocarcinoma].

Zhonghua yi xue za zhi·2022

Same author

[The variation of serum uric acid levels among patients with myocardial infarction treated with ticagrelor and the association between serum uric acid and platelet reactivity].

Zhonghua xin xue guan bing za zhi·2021

Same author

[Clonal-related transformation from Waldenström macroglobulinemia to diffuse large B cell lymphoma during the treatment of ibrutinib: a case report and literature review].

Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi·2020

Same author

[Associations between postprocedural D-dimer, hs-CRP, LDL-C levels and prognosis of acute myocardial infarction patients treated by percutaneous coronary intervention].

Zhonghua xin xue guan bing za zhi·2020

Area of Science:

Genetics
Epigenetics
Cancer Biology

Background:

Global DNA hypomethylation is observed in tumor cells and linked to genomic instability.
Defects in DNA methylation may contribute to colorectal tumor cell line instability.
Hypomethylation is associated with chromosomal abnormalities in ICF syndrome and with demethylating agents.

Purpose of the Study:

To investigate the role of DNA methylation in maintaining genome stability.
To determine the mutation rates in cells lacking major DNA methyltransferase (Dnmt1).

Main Methods:

Generated murine embryonic stem cells nullizygous for the Dnmt1 gene.
Assessed mutation rates at the endogenous hypoxanthine phosphoribosyltransferase (Hprt) gene and a viral thymidine kinase (tk) transgene.

Related Experiment Videos

Analyzed the types of mutations, including gene deletions, mitotic recombination, and chromosomal loss.

Main Results:

Dnmt1-deficient murine embryonic stem cells showed significantly elevated mutation rates at both Hprt and tk loci.
Gene deletions were the predominant mutation type observed.
Mitotic recombination or chromosomal loss with duplication were the major causes of tk deletions.

Conclusions:

Mammalian DNA methylation, specifically via Dnmt1, plays a crucial role in maintaining genome stability.
Loss of DNA methylation can lead to increased mutation rates and chromosomal instability.
These findings support the hypothesis that genome-wide demethylation contributes to carcinogenesis.