Abstract
Mammalian terminal deoxyribonucleotidyl transferase (TDT) catalyzes the non-template-directed polymerization of deoxyribonucleoside triphosphates and has a key role in V(D)J recombination during lymphocyte and repertoire development. Over 90% of leukemic cells in acute lymphocytic leukemia and approximately 30% of leukemic cells in the chronic myelogenous leukemia crisis show elevated TDT activity. This finding is connected to a poor prognosis and response to chemotherapy and reduced survival time. On the other hand, recent data indicated that TDT is not the only terminal deoxyribonucleotidyl transferase in mammalian cells. Its close relative, DNA polymerase (pol) pol λ can synthesize DNA both in a template dependent (DNA polymerase) and template-independent (terminal deoxyribonucleotidyl transferase) fashion. Pol λ might be involved in the nonhomologous end-joining (NHEJ) recombinational repair pathway of DNA double strand breaks (DSBs). Specific inhibitors of these enzymes hold the potential to be developed into a novel class of antitumoral agents. In this review, we will summarize the recent advances in the synthesis and characterization of the first classes of specific inhibitors of mammalian terminal transferases and their potential applications.
Keywords: DNA double strand breaks (DSB), Leukemias, transcriptional factors, DNA polymerases, Nucleoside Inhibitors, Aryl Diketo Hexenoic Acid, Resveratrol
Current Medicinal Chemistry
Title: Human Terminal Deoxynucleotidyl Transferases as Novel Targets for Anticancer Chemotherapy
Volume: 13 Issue: 20
Author(s): Giovanni Maga and Roberto Di Santo
Affiliation:
Keywords: DNA double strand breaks (DSB), Leukemias, transcriptional factors, DNA polymerases, Nucleoside Inhibitors, Aryl Diketo Hexenoic Acid, Resveratrol
Abstract: Mammalian terminal deoxyribonucleotidyl transferase (TDT) catalyzes the non-template-directed polymerization of deoxyribonucleoside triphosphates and has a key role in V(D)J recombination during lymphocyte and repertoire development. Over 90% of leukemic cells in acute lymphocytic leukemia and approximately 30% of leukemic cells in the chronic myelogenous leukemia crisis show elevated TDT activity. This finding is connected to a poor prognosis and response to chemotherapy and reduced survival time. On the other hand, recent data indicated that TDT is not the only terminal deoxyribonucleotidyl transferase in mammalian cells. Its close relative, DNA polymerase (pol) pol λ can synthesize DNA both in a template dependent (DNA polymerase) and template-independent (terminal deoxyribonucleotidyl transferase) fashion. Pol λ might be involved in the nonhomologous end-joining (NHEJ) recombinational repair pathway of DNA double strand breaks (DSBs). Specific inhibitors of these enzymes hold the potential to be developed into a novel class of antitumoral agents. In this review, we will summarize the recent advances in the synthesis and characterization of the first classes of specific inhibitors of mammalian terminal transferases and their potential applications.
Export Options
About this article
Cite this article as:
Maga Giovanni and Di Santo Roberto, Human Terminal Deoxynucleotidyl Transferases as Novel Targets for Anticancer Chemotherapy, Current Medicinal Chemistry 2006; 13 (20) . https://dx.doi.org/10.2174/092986706777935087
DOI https://dx.doi.org/10.2174/092986706777935087 |
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
-
Recent Advances in Treatment Approaches of Mucopolysaccharidosis VI
Current Pharmaceutical Biotechnology Apo-E4 Allele in Conjunction with Aβ42 and Tau in CSF: Biomarker for Alzheimers Disease
Current Alzheimer Research Alzheimers Disease (AD) and Mild Cognitive Impairment (MCI) Patients are Characterized by Increased BDNF Serum Levels
Current Alzheimer Research Five Decades of Cuprizone, an Updated Model to Replicate Demyelinating Diseases
Current Neuropharmacology Maintaining Plasma Fibrinogen Levels and Fibrinogen Replacement Therapies for Treatment of Intracranial Hemorrhage
Current Drug Targets Integration of Cognitive Tests and Resting State fMRI for the Individual Identification of Mild Cognitive Impairment
Current Alzheimer Research In Vivo Human Amyloid Imaging
Current Alzheimer Research An Intelligent Three-dimensional Ultrasound Program for Rapidly Imaging of the Fetal Cranial Mid-sagittal Plane
Current Medical Imaging Myotonic Dystrophies 1 and 2: Complex Diseases with Complex Mechanisms
Current Genomics Drugs Targeting Parasite Lysosomes
Current Pharmaceutical Design Green Tea, A Medicinal Food with Promising Neurological Benefits
Current Neuropharmacology Dural Venous Sinuses: What We Need to Know
Current Medical Imaging Recent Advances and Patents on Nanoscale Systems and Triggerable Drug Delivery in Medical Devices
Recent Patents on Biomedical Engineering (Discontinued) Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies
Current Pharmaceutical Design Hepatocyte Growth Factor (HGF): Neurotrophic Functions and Therapeutic Implications for Neuronal Injury/Diseases
Current Signal Transduction Therapy Down-Regulation of Angiogenic Inhibitors: A Potential Pathogenic Mechanism for Diabetic Complications
Current Diabetes Reviews A Review of Various Machine Learning Techniques for Brain Tumor Detection from MRI Images
Current Medical Imaging Neurotrophic Factors for the Investigation and Treatment of Movement Disorders
Current Medicinal Chemistry - Central Nervous System Agents Diagnosis and Prognosis of Fetal Cardiomyopathies: A Review
Current Pharmaceutical Design A Translational View of Peptide Treatment of Neurological Disorders
Current Medicinal Chemistry