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Molecular and Cellular Biology, June 2007, p. 3891-3899, Vol. 27, No. 11
0270-7306/07/$08.00+0     doi:10.1128/MCB.00036-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Biological Functions of DNA Methyltransferase 1 Require Its Methyltransferase Activity{triangledown} ,{dagger}

Marc Damelin and Timothy H. Bestor*

Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, 701 W. 168th St., New York, New York 10032

Received 8 January 2007/ Returned for modification 1 March 2007/ Accepted 12 March 2007

DNA methyltransferase 1 (DNMT1) has been reported to interact with a wide variety of factors and to contain intrinsic transcriptional repressor activity. When a conservative point mutation was introduced at the key catalytic residue, mutant DNMT1 failed to rescue any of the phenotypes of Dnmt1-null embryonic stem (ES) cells, which indicated that the biological functions of DNMT1 are exerted through the methylation of DNA. ES cells that expressed the mutant protein did not survive differentiation. Intracisternal A-particle family retrotransposons were no longer methylated and were transcribed at high levels. The proper localization of DNMT1 depended on normal genomic methylation, and we discuss the implications of this finding for epigenetic dysregulation in cancer.

* Corresponding author. Mailing address: Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-5331. Fax: (212) 740-0992. E-mail: THB12{at}columbia.edu

{triangledown} Published ahead of print on 19 March 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, June 2007, p. 3891-3899, Vol. 27, No. 11
0270-7306/07/$08.00+0     doi:10.1128/MCB.00036-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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