Abstract
The cellular genome is constantly subject to DNA damage caused by endogenous factors or exogenously by damaging agents such as ionizing radiation or various anticancer agents. The base excision repair (BER) enzyme, DNA polymerase β, and the polymerases involved in translesion synthesis (TLS) have been shown to contribute to cellular tolerance and repair of DNA lesions by anticancer treatments, particularly the platinum cytotoxic drugs. Moreover, there is robust preclinical evidence linking alterations in DNA pol β and TLS polymerase levels to cancer. DNA polymerases may therefore be potential targets to increase the sensitivity of cancer cells to chemotherapy drugs. In this article, the physical and chemical properties of DNA polymerase β and the translesion synthesis polymerases are reviewed with a view to identifying how they may act as targets for anticancer treatment. The potential clinical role of new DNA polymerase inhibitors is discussed and how they may be combined with conventional cytotoxic agents.
Keywords: Base excision repair, cisplatin, DNA damage repair, DNA polymerase, oxaliplatin, radiotherapy, translesion synthesis
Current Molecular Pharmacology
Title: Biological Relevance of DNA Polymerase Beta and Translesion Synthesis Polymerases to Cancer and its Treatment
Volume: 5
Author(s): Nils H. Nicolay, Thomas Helleday and Ricky A. Sharma
Affiliation:
Keywords: Base excision repair, cisplatin, DNA damage repair, DNA polymerase, oxaliplatin, radiotherapy, translesion synthesis
Abstract: The cellular genome is constantly subject to DNA damage caused by endogenous factors or exogenously by damaging agents such as ionizing radiation or various anticancer agents. The base excision repair (BER) enzyme, DNA polymerase β, and the polymerases involved in translesion synthesis (TLS) have been shown to contribute to cellular tolerance and repair of DNA lesions by anticancer treatments, particularly the platinum cytotoxic drugs. Moreover, there is robust preclinical evidence linking alterations in DNA pol β and TLS polymerase levels to cancer. DNA polymerases may therefore be potential targets to increase the sensitivity of cancer cells to chemotherapy drugs. In this article, the physical and chemical properties of DNA polymerase β and the translesion synthesis polymerases are reviewed with a view to identifying how they may act as targets for anticancer treatment. The potential clinical role of new DNA polymerase inhibitors is discussed and how they may be combined with conventional cytotoxic agents.
Export Options
About this article
Cite this article as:
H. Nicolay Nils, Helleday Thomas and A. Sharma Ricky, Biological Relevance of DNA Polymerase Beta and Translesion Synthesis Polymerases to Cancer and its Treatment, Current Molecular Pharmacology 2012; 5 (1) . https://dx.doi.org/10.2174/1874467211205010054
DOI https://dx.doi.org/10.2174/1874467211205010054 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
- 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
-
Metastasis Suppressors: Basic and Translational Advances
Current Pharmaceutical Biotechnology Tumour Cytochrome P450 and Drug Activation
Current Pharmaceutical Design Duloxetine in the Treatment of Depression: An Overview
Central Nervous System Agents in Medicinal Chemistry PI3K Pathway Inhibitors: Better Not Left Alone
Current Pharmaceutical Design The Role of ABC Transporters in Protecting Cells from Bilirubin Toxicity
Current Pharmaceutical Design Oxidative Stress, Redox Signaling and Cancer Chemoresistance: Putting Together the Pieces of the Puzzle
Current Medicinal Chemistry Interactions of Metal Ions with DNA, Its Constituents and Derivatives, which may be Relevant for Anticancer Research
Current Topics in Medicinal Chemistry Cancer Gene Therapy with Tissue Inhibitors of Metalloproteinases (TIMPs)
Current Gene Therapy The Anticancer Properties of Silibinin: Its Molecular Mechanism and Therapeutic Effect in Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry DLEU1: A Functional Long Noncoding RNA in Tumorigenesis
Current Pharmaceutical Design The Complexity of Aging: Cancer Risk Among Elderly People and Infectious Risk Among Those with Cancer
Anti-Cancer Agents in Medicinal Chemistry Controlled-release Particulate Cytokine Adjuvants for Cancer Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets The Prominent Role of Protein-Based Delivery Systems on the Development of Cancer Treatment
Current Pharmaceutical Design Advances of Phenoxazines: Synthesis, Reactivity and Their Medicinal Applications
Current Medicinal Chemistry Isothiocyanates in the Chemoprevention of Bladder Cancer
Current Drug Metabolism Phage Display Applications for Molecular Imaging
Current Pharmaceutical Biotechnology Urine Cells-derived iPSCs: An Upcoming Frontier in Regenerative Medicine
Current Medicinal Chemistry Function Analysis of Human Protein Interactions Based on a Novel Minimal Loop Algorithm
Current Bioinformatics Rational Combination of Targeted Therapies As A Strategy to Overcome The Mechanisms of Resistance to Inhibitors of EGFR Signaling
Current Pharmaceutical Design Proteinase-Activated Receptor-2: Physiological and Pathophysiological Roles
Current Medicinal Chemistry - Cardiovascular & Hematological Agents