Work

A mutantHpallmethyltransferase functions as a mutator enzyme

Year: 1995

Type: article

Abstract: DNA (cytosine-5)-methyltransferases can cause deamination of cytosine when the cofactor S-adenosylmethionine (AdoMet) is limiting and thus function as sequence-specific C-->U mutator enzymes. Here we explored whether mutations causing inactivation of the cofactor binding activity of the HpaII methyltransferase, thus mimicking conditions of limiting AdoMet concentration, could convert a DNA methyltransferase to a C-->U mutator enzyme. We created two mutator enzymes from the HpaII methyltransferase (F38S and G40D) which both showed enhanced cytosine deamination activities in vitro and in vivo. Interestingly, the G:U mispairs generated by these enzymes were not repaired completely in bacteria equipped with uracil-DNA glycosylase-initiated repair machinery, giving rise to a potent mutator phenotype. This is the first report showing the creation of mutator enzymes from a DNA methyltransferase and the demonstration of their mutagenicity in living cells.

Source: Nucleic Acids Research

DOI: 10.1093/nar/23.21.4275

Authors: Jiang-Cheng Shen, Jean-Marc Zingg, Allen S. Yang, Christoph Schmutte, Peter A. Jones

Institutions: University of Southern California, USC Norris Comprehensive Cancer Center

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Cancer Institute

Award: DNA METHYLATION IN DEVELOPMENT AND CANCER