Abstract
DNA is modified by many mutagens, including reactive oxygen species (ROS). When ROS react with DNA, various kinds of modified base and/or sugar moieties are produced. One of the most important oxidative DNA lesions is 7,8-dihydro-8-oxoguanine (8-oxo-G). Contrary to normal deoxyguanosine, 8-oxo-G favors a syn conformation, enabling it to form a Hoogsteen base pair with adenine which resembles a normal Watson-Crick base pair in shape and geometry. As a consequence, most human DNA polymerases (pols) studied so far show significant error-prone bypass of 8-oxo-G. The 1,2-dihydro-2-oxoadenine (2-OH-A) is another common DNA lesion produced by ROS. 2-OH-A possesses significant mutagenic potential in living cells. When challenged with a 2-OH-A lesion on the template, DNA pols often misinsert G and C nucleotides, with various efficiencies depending upon the sequence context. We have recently shown that human DNA pol λ is extremely efficient in performing error-free bypass of both 8-oxo-G and 2-OH-A lesions, and that its efficiency is positively modulated by the auxiliary factors proliferating cell nuclear antigen and replication protein A. In this review we will summarize the most recent advancements in the field of oxidative DNA damage tolerance with special emphasis on the pro- and anti-mutagenic roles of DNA pols and auxiliary proteins.
Current Molecular Pharmacology
Title: DNA Polymerases and Oxidative Damage: Friends or Foes?
Volume: 1
Author(s): A. Amoroso, E. Crespan, U. Wimmer, U. Hubscher and G. Maga
Affiliation:
Abstract: DNA is modified by many mutagens, including reactive oxygen species (ROS). When ROS react with DNA, various kinds of modified base and/or sugar moieties are produced. One of the most important oxidative DNA lesions is 7,8-dihydro-8-oxoguanine (8-oxo-G). Contrary to normal deoxyguanosine, 8-oxo-G favors a syn conformation, enabling it to form a Hoogsteen base pair with adenine which resembles a normal Watson-Crick base pair in shape and geometry. As a consequence, most human DNA polymerases (pols) studied so far show significant error-prone bypass of 8-oxo-G. The 1,2-dihydro-2-oxoadenine (2-OH-A) is another common DNA lesion produced by ROS. 2-OH-A possesses significant mutagenic potential in living cells. When challenged with a 2-OH-A lesion on the template, DNA pols often misinsert G and C nucleotides, with various efficiencies depending upon the sequence context. We have recently shown that human DNA pol λ is extremely efficient in performing error-free bypass of both 8-oxo-G and 2-OH-A lesions, and that its efficiency is positively modulated by the auxiliary factors proliferating cell nuclear antigen and replication protein A. In this review we will summarize the most recent advancements in the field of oxidative DNA damage tolerance with special emphasis on the pro- and anti-mutagenic roles of DNA pols and auxiliary proteins.
Export Options
About this article
Cite this article as:
Amoroso A., Crespan E., Wimmer U., Hubscher U. and Maga G., DNA Polymerases and Oxidative Damage: Friends or Foes?, Current Molecular Pharmacology 2008; 1 (2) . https://dx.doi.org/10.2174/1874467210801020162
DOI https://dx.doi.org/10.2174/1874467210801020162 |
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
-
Adenovirus Mediated Herpes Simplex Virus-Thymidine Kinase/Ganciclovir Gene Therapy for Resectable Malignant Glioma
Current Gene Therapy Fork Head Transcription Factors
Current Genomics Imaging Malignant Gliomas with 99mTc-MIBI Brain Single-Photon Emission Computed Tomography
Current Medical Imaging Endocannabinoid System in Neurological Disorders
Recent Patents on CNS Drug Discovery (Discontinued) How Early is Too Early? A Review of Infant Seizure Surgery Literature
Current Pediatric Reviews Modulation of Aquaporins by Dietary Patterns and Plant Bioactive Compounds
Current Medicinal Chemistry Antioxidant SkQ1 Alleviates Signs of Alzheimer’s Disease-like Pathology in Old OXYS Rats by Reversing Mitochondrial Deterioration
Current Alzheimer Research Development of a Registry for Down Syndrome in the Gulf Area of the Middle East
Applied Clinical Research, Clinical Trials and Regulatory Affairs Neurotuberculosis: An Overview
Central Nervous System Agents in Medicinal Chemistry Clinical Pharmacology of Phenobarbital in Neonates: Effects, Metabolism and Pharmacokinetics
Current Pediatric Reviews Diagnostic Accuracy of Sagittal TSE-T2W, Variable Flip Angle 3D TSET2W and High-resolution 3D Heavily T2W Sequences for the Stenosis of Two Localizations: The Cerebral Aqueduct and the Superior Medullary Velum
Current Medical Imaging Antifungal Agents in Hematopoietic Stem Cell Transplantation
Current Pharmaceutical Design Pharmacological Treatment of Mild Cognitive Impairment as a Prodromal Syndrome of Alzheimer´s Disease
Current Neuropharmacology Early Timing of Endovascular Treatment for Aneurysmal Subarachnoid Hemorrhage Achieves Improved Outcomes
Current Neurovascular Research Perioperative Management of Intracranial Aneurysm and Subarachnoid Hemorrhage
Current Pharmaceutical Design Patent Selections
Recent Patents on Materials Science Cerebrospinal Fluid Flow Dynamics in Multiple Sclerosis Patients through Phase Contrast Magnetic Resonance Imaging
Current Neurovascular Research The Frequency of Thrombotic Events Among Adults Given Antifibrinolytic Drugs for Spontaneous Bleeding: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials
Current Drug Safety “Epileptic Encephalopathy” of Infancy and Childhood: Electro-Clinical Pictures and Recent Understandings
Current Neuropharmacology Early Brain Injury or Vasospasm? An Overview of Common Mechanisms
Current Drug Targets