Abstract
The clustered DNA lesions are a characteristic feature of ionizing radiation and are defined as two or more damage sites formed within 20 bps after the passage of a single radiation track. The clustered DNA lesions are divided into two major groups: double-stranded breaks (DSBs) and non-DSB clusters also known as Oxidatively-induced Clustered DNA Lesions (OCDLs), which could involve either two opposing strands or the same strand. As irradiation is gaining greater interest in cancer treatment as well as in imaging techniques, the detailed knowledge of its genotoxicity and the mechanisms of repair of radiation-induced DNA damage remain issues to explore. In this review we look at the ways the cell copes with clustered DNA lesions, especially with 5′,8-cyclo-2′-deoxypurines. As the base excision repair deals with isolated lesions, complex damage is more difficult to repair. Depending on the number of lesions within a cluster, their types and mutual distribution, long-patch BER or NER are activated. During the repair of opposing lesions, DSBs could be generated, which are repaired either by nonhomologous end joining (NHEJ) or homologous recombination (HR). The repair of individual lesions within a cluster progresses gradually. This slower processing of particular damage might lead to severe biological consequences such as misrepair, mutations and chromosomal rearrengement as it enhances the plausibility of a cluster encountering a replication fork prior to its repair. The consequences of clustered DNA lesions on cell survival and their relevance to the efficacy and safety of radiotherapy and radiodiagnosis will also be discussed.
Keywords: Clustered DNA lesions, 5′, 8-cyclo-2′-deoxypurines, base excision repair, ionizing radiation, radiotherapy, tandem lesions.
Current Medicinal Chemistry
Title:The Clustered DNA Lesions – Types, Pathways of Repair and Relevance to Human Health
Volume: 25 Issue: 23
Author(s): Barbara Bukowska*Boleslaw T. Karwowski
Affiliation:
- Food Science Department, Faculty of Pharmacy, Medical University of Lodz, Lodz,Poland
Keywords: Clustered DNA lesions, 5′, 8-cyclo-2′-deoxypurines, base excision repair, ionizing radiation, radiotherapy, tandem lesions.
Abstract: The clustered DNA lesions are a characteristic feature of ionizing radiation and are defined as two or more damage sites formed within 20 bps after the passage of a single radiation track. The clustered DNA lesions are divided into two major groups: double-stranded breaks (DSBs) and non-DSB clusters also known as Oxidatively-induced Clustered DNA Lesions (OCDLs), which could involve either two opposing strands or the same strand. As irradiation is gaining greater interest in cancer treatment as well as in imaging techniques, the detailed knowledge of its genotoxicity and the mechanisms of repair of radiation-induced DNA damage remain issues to explore. In this review we look at the ways the cell copes with clustered DNA lesions, especially with 5′,8-cyclo-2′-deoxypurines. As the base excision repair deals with isolated lesions, complex damage is more difficult to repair. Depending on the number of lesions within a cluster, their types and mutual distribution, long-patch BER or NER are activated. During the repair of opposing lesions, DSBs could be generated, which are repaired either by nonhomologous end joining (NHEJ) or homologous recombination (HR). The repair of individual lesions within a cluster progresses gradually. This slower processing of particular damage might lead to severe biological consequences such as misrepair, mutations and chromosomal rearrengement as it enhances the plausibility of a cluster encountering a replication fork prior to its repair. The consequences of clustered DNA lesions on cell survival and their relevance to the efficacy and safety of radiotherapy and radiodiagnosis will also be discussed.
Export Options
About this article
Cite this article as:
Bukowska Barbara *, Karwowski T. Boleslaw , The Clustered DNA Lesions – Types, Pathways of Repair and Relevance to Human Health, Current Medicinal Chemistry 2018; 25 (23) . https://dx.doi.org/10.2174/0929867325666180226110502
DOI https://dx.doi.org/10.2174/0929867325666180226110502 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Angiogenesis Markers in Gynecological Tumors and Patents for Anti- Angiogenic Approach: Review
Recent Patents on Anti-Cancer Drug Discovery Nanoparticles for Gene Delivery: A Brief Patent Review
Recent Patents on Drug Delivery & Formulation The Promise of miRNA Replacement Therapy for Hepatocellular Carcinoma
Current Gene Therapy The Chemopreventive and Chemotherapeutic Potentials of Tea Polyphenols
Current Pharmaceutical Biotechnology Cancer/Testis Antigens Trigger Epithelial-Mesenchymal Transition and Genesis of Cancer Stem-Like Cells
Current Pharmaceutical Design The Pro-Survival Function of Akt Kinase can be Overridden or Altered to Contribute to Induction of Apoptosis
Current Cancer Drug Targets HER2 in the Era of Molecular Medicine: A Review
Current Cancer Therapy Reviews Ceramide and Sphingosine-1-Phosphate in Cell Death Pathways : Relevance to the Pathogenesis of Alzheimer's Disease
Current Alzheimer Research Viral Vectors for Cancer Gene Therapy: Viral Dissemination and Tumor Targeting
Current Gene Therapy Nutraceuticals for Promoting Longevity
Current Nutraceuticals Betulinic Acid as a Potent and Complex Antitumor Phytochemical: A Minireview
Anti-Cancer Agents in Medicinal Chemistry Inflammation and Antiangiogenesis in Cancer
Current Medicinal Chemistry Bugs and Drugs: Oncolytic Virotherapy in Combination with Chemotherapy
Current Pharmaceutical Biotechnology Cyclooxygenase-2 Inhibition and Gastric Cancer
Current Pharmaceutical Design Targeting the Tumor Proteasome as a Mechanism to Control the Synthesis and Bioactivity of Matrix Macromolecules
Current Molecular Medicine Enhancement of Epidermal Basement Membrane Formation by Synthetic Inhibitors of Extracellular Matrix-degrading Enzymes
Current Tissue Engineering (Discontinued) The Mouse In Cancer Research Past, Present, Future
Current Genomics Targeting the Programmed Cell Death-1 Pathway in Genitourinary Tumors: Current Progress and Future Perspectives
Current Drug Metabolism Phytochemical Screening and In-Vitro Antibacterial and Anticancer Activity of Crude Extract of <i>Matricaria aurea</i>
Current Pharmaceutical Design Intracellular Delivery of Potential Therapeutic Genes: Prospects in Cancer Gene Therapy
Current Gene Therapy