Int J Biochem Mol Biol 2011;2(1):58-66
Review Article
DNA Methyl Transferase 1: Regulatory mechanisms and implications in health and
disease
Sirano Dhe-Paganon, Farisa Syeda, Lawrence Park
Department of Physiology, University of Toronto, Canada; Department of Cell and Systems Biology, University of Toronto, Canada.
Received January 12, 2011; accepted January 25, 2010; Epub January 30, 2010; published February 15, 2011
Abstract: DNA methylation serves as the principal form of post-replicative epigenetic modification. It is intricately involved in gene regulation
and silencing in eukaryotic cells, making significant contributions to cell phenotype. Much of it is mitotically inherited; some is passed on from
one filial generation to the next. Establishment and maintenance of DNA methylation patterns in mammals is governed by three catalytically
active DNA methyltransferases – DNMT3a, DNMT3b and DNMT1. While the first two are responsible mainly for de novo methylation, DNMT1
maintains the methylation patterns by preferentially catalyzing S-adenosyl methionine-dependant transfer of a methyl group to cytosine at
hemimethylated CpG sites generated as a result of semi-conservative DNA replication. DNMT1 contains numerous regulatory domains that
fine-tune associated catalytic activities, deregulation of which is observed in several diseases including cancer. In this minireview, we analyze
the regulatory mechanisms of various subdomains of DNMT1 protein and briefly discuss its pathophysiological and pharmacological
implications. A better understanding of DNMT1 function and structure will likely reveal new applications in the treatment of associated
diseases. (IJBMB1101002).
Keywords: DNMT1, catalytic regulation, epigenetics, disease implications
Full Text PDF
Address all correspondence to:
Dr. Sirano Dhe-Paganon
Department of Physiology, University of Toronto
Principal Investigator, Structural Genomics Consortium
101 College Street, MaRS South Tower, Suite 700, Toronto, ON M5G 1L7
Tel: (001) 416-946-3876
Fax: (001) 416-946-0880
E-mail: sirano.dhepaganon@utoronto.ca
Review Article
DNA Methyl Transferase 1: Regulatory mechanisms and implications in health and
disease
Sirano Dhe-Paganon, Farisa Syeda, Lawrence Park
Department of Physiology, University of Toronto, Canada; Department of Cell and Systems Biology, University of Toronto, Canada.
Received January 12, 2011; accepted January 25, 2010; Epub January 30, 2010; published February 15, 2011
Abstract: DNA methylation serves as the principal form of post-replicative epigenetic modification. It is intricately involved in gene regulation
and silencing in eukaryotic cells, making significant contributions to cell phenotype. Much of it is mitotically inherited; some is passed on from
one filial generation to the next. Establishment and maintenance of DNA methylation patterns in mammals is governed by three catalytically
active DNA methyltransferases – DNMT3a, DNMT3b and DNMT1. While the first two are responsible mainly for de novo methylation, DNMT1
maintains the methylation patterns by preferentially catalyzing S-adenosyl methionine-dependant transfer of a methyl group to cytosine at
hemimethylated CpG sites generated as a result of semi-conservative DNA replication. DNMT1 contains numerous regulatory domains that
fine-tune associated catalytic activities, deregulation of which is observed in several diseases including cancer. In this minireview, we analyze
the regulatory mechanisms of various subdomains of DNMT1 protein and briefly discuss its pathophysiological and pharmacological
implications. A better understanding of DNMT1 function and structure will likely reveal new applications in the treatment of associated
diseases. (IJBMB1101002).
Keywords: DNMT1, catalytic regulation, epigenetics, disease implications
Full Text PDF
Address all correspondence to:
Dr. Sirano Dhe-Paganon
Department of Physiology, University of Toronto
Principal Investigator, Structural Genomics Consortium
101 College Street, MaRS South Tower, Suite 700, Toronto, ON M5G 1L7
Tel: (001) 416-946-3876
Fax: (001) 416-946-0880
E-mail: sirano.dhepaganon@utoronto.ca
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