Abstract
DNA methylation is an epigenetic event involved in a variety array of processes that may be the foundation of genetic phenomena and diseases. DNA methyltransferase is a key enzyme for cytosine methylation in DNA, and can be divided into two functional families (Dnmt1 and Dnmt3) in mammals. All mammalian DNA methyltransferases are encoded by their own single gene, and consisted of catalytic and regulatory regions (except Dnmt2). Via interactions between functional domains in the regulatory or catalytic regions and other adaptors or cofactors, DNA methyltransferases can be localized at selective areas (specific DNA/nucleotide sequence) and linked to specific chromosome status (euchromatin/ heterochromatin, various histone modification status). With assistance from UHRF1 and Dnmt3L or other factors in Dnmt1 and Dnmt3a/Dnmt3b, mammalian DNA methyltransferases can be recruited, and then specifically bind to hemimethylated and unmethylated double-stranded DNA sequence to maintain and de novo setup patterns for DNA methylation. Complicated enzymatic steps catalyzed by DNA methyltransferases include methyl group transferred from cofactor Ado-Met to C5 position of the flipped-out cytosine in targeted DNA duplex. In the light of the fact that different DNA methyltransferases are divergent in both structures and functions, and use unique reprogrammed or distorted routines in development of diseases, design of new drugs targeting specific mammalian DNA methyltransferases or their adaptors in the control of key steps in either maintenance or de novo DNA methylation processes will contribute to individually treating diseases related to DNA methyltransferases.
Keywords: DNA methyltransferase, epigenetics, enzyme catalysis, protein-DNA interactions, DNA MTase, replication- foci targeting, RFT, targeting sequence, TS, methyl-CpG binding protein-2, MeCP2, methyl-CpG binding domain protein, MBD2, MBD3, HDAC1, histone deacetylase-1, HDAC2, H3-K9 methyltransferase, Suv39h1, HP1b, DNMT3A2, ATRX, alpha-thalassemia and mental retardation on X chromosome, TRDMT1, tRNA aspartic acid methyltransferase 1, S-adenosyl-L-homocysteine, UHRF1
Current Medicinal Chemistry
Title: Molecular and Enzymatic Profiles of Mammalian DNA Methyltransferases: Structures and Targets for Drugs
Volume: 17 Issue: 33
Author(s): F. Xu, C. Mao, Y. Ding, C. Rui, L. Wu, A. Shi, H. Zhang, L. Zhang and Z. Xu
Affiliation:
Keywords: DNA methyltransferase, epigenetics, enzyme catalysis, protein-DNA interactions, DNA MTase, replication- foci targeting, RFT, targeting sequence, TS, methyl-CpG binding protein-2, MeCP2, methyl-CpG binding domain protein, MBD2, MBD3, HDAC1, histone deacetylase-1, HDAC2, H3-K9 methyltransferase, Suv39h1, HP1b, DNMT3A2, ATRX, alpha-thalassemia and mental retardation on X chromosome, TRDMT1, tRNA aspartic acid methyltransferase 1, S-adenosyl-L-homocysteine, UHRF1
Abstract: DNA methylation is an epigenetic event involved in a variety array of processes that may be the foundation of genetic phenomena and diseases. DNA methyltransferase is a key enzyme for cytosine methylation in DNA, and can be divided into two functional families (Dnmt1 and Dnmt3) in mammals. All mammalian DNA methyltransferases are encoded by their own single gene, and consisted of catalytic and regulatory regions (except Dnmt2). Via interactions between functional domains in the regulatory or catalytic regions and other adaptors or cofactors, DNA methyltransferases can be localized at selective areas (specific DNA/nucleotide sequence) and linked to specific chromosome status (euchromatin/ heterochromatin, various histone modification status). With assistance from UHRF1 and Dnmt3L or other factors in Dnmt1 and Dnmt3a/Dnmt3b, mammalian DNA methyltransferases can be recruited, and then specifically bind to hemimethylated and unmethylated double-stranded DNA sequence to maintain and de novo setup patterns for DNA methylation. Complicated enzymatic steps catalyzed by DNA methyltransferases include methyl group transferred from cofactor Ado-Met to C5 position of the flipped-out cytosine in targeted DNA duplex. In the light of the fact that different DNA methyltransferases are divergent in both structures and functions, and use unique reprogrammed or distorted routines in development of diseases, design of new drugs targeting specific mammalian DNA methyltransferases or their adaptors in the control of key steps in either maintenance or de novo DNA methylation processes will contribute to individually treating diseases related to DNA methyltransferases.
Export Options
About this article
Cite this article as:
Xu F., Mao C., Ding Y., Rui C., Wu L., Shi A., Zhang H., Zhang L. and Xu Z., Molecular and Enzymatic Profiles of Mammalian DNA Methyltransferases: Structures and Targets for Drugs, Current Medicinal Chemistry 2010; 17 (33) . https://dx.doi.org/10.2174/092986710793205372
DOI https://dx.doi.org/10.2174/092986710793205372 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
PEDF in Angiogenic Eye Diseases
Current Molecular Medicine Enhancing the Cytotoxic Activity of Novel Targeted Therapies – Is There a Role for a Combinatorial Approach?
Current Clinical Pharmacology Sirolimus and its Analogs and its Effects on Vascular Diseases
Current Pharmaceutical Design Increased Paternal Age and Child Health and Development
Current Pediatric Reviews Insights into the Pathogenesis and Intervention of Atherosclerosis
Vascular Disease Prevention (Discontinued) Gene Therapy in Plastic and Reconstructive Surgery
Current Gene Therapy Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current Pharmaceutical Design Morphologic and Molecular Backgrounds for Personalized Management of Genito-Urinary Cancers: An Overview
Current Drug Targets Photosensitizer Nanoparticles for Photodynamic Therapy
Current Bioactive Compounds Human Platelet Acetylcholinesterase Inhibition by Cyclophosphamide: A Combined Experimental and Computational Approach
CNS & Neurological Disorders - Drug Targets Therapeutic Strategies to Target Multiple Kinases in Glioblastoma
Anti-Cancer Agents in Medicinal Chemistry Multiple-Target Drugs: Inhibitors of Heat Shock Protein 90 and of Histone Deacetylase
Current Drug Targets Molecular Genetics and Targeted Therapy in Hepatocellular Carcinoma
Current Cancer Drug Targets Microenvironmental Regulation of Cancer Stem Cell Phenotypes
Current Stem Cell Research & Therapy MicroRNAs as Diagnostic, Prognostic and Predictive Biomarkers of Ovarian Cancer
Recent Patents on Biomarkers Lactoferrin Derived Peptides: Mechanisms of Action and their Perspectives as Antimicrobial and Antitumoral Agents
Mini-Reviews in Medicinal Chemistry Editorial (Personalized Medicine in the Age of Pharmacoproteomics: A Close up on India and Need for Social Science Engagement for Responsible Innovation in Post-Proteomic Biology)
Current Pharmacogenomics and Personalized Medicine Medicinal Compound Celastrol As a Potential Clinical Anticancer Drug: Lessons Learned From Preclinical Studies
Clinical Cancer Drugs Inhibition of RET Activated Pathways: Novel Strategies for Therapeutic Intervention in Human Cancers
Current Pharmaceutical Design Keeping the Balance Between Proliferation and Differentiation:The Primary Cilium
Current Genomics