Abstract
The transmission of genetic information relies on a coordinated network of cell cycle controls. Abnormalities in this network can result in genomic instability and lead to the transformation of normal cells into cancer cells. Chromosomal DNA replication is not only central to cellular division but also plays a crucial role in the maintenance of genomic integrity. DNA replication errors increase genetic instability, and may be a causative factor in diseases such as cancer and neuronal disorders. Replication in eukaryotes initiates from discrete genomic regions, termed origins, according to a strict, often tissue-specific, temporal program. The genetic program that controls activation of replication origins in mammalian cells has still not been elucidated. There is evidence that specification of replication sites and timing of replication are dynamic processes that are regulated by tissue-specific and developmental cues and that are responsive to epigenetic modifications. Here, we focus on the spatiotemporal regulation of DNA replication in the human genome. There is growing evidence that chromosome band patterns and epigenetic transformation of chromatin influence the timing of replication. On the basis of this evidence, we propose that the chromatin regions showing switches in replication timing from early to late in S phase are correlated with chromosome band boundaries. These chromatin regions generally display transitions in GC contents and include more non-B-form DNA structures than other genomic regions. We also examine here the effect of changes in replication timing on genomic stability and the possible role of replication timing in the etiology of diseases such as cancer. Replication timing assays are one of many promising techniques under investigation that may in future allow much earlier cancer detection than is possible today.
Keywords: DNA replication timing, human genome, chromosomal bands, genomic instability, non-B-DNA structure, human disease
Current Medicinal Chemistry
Title: Spatiotemporal Regulation of DNA Replication in the Human Genome and its Association with Genomic Instability and Disease
Volume: 17 Issue: 3
Author(s): Yoshihisa Watanabe and Masato Maekawa
Affiliation:
Keywords: DNA replication timing, human genome, chromosomal bands, genomic instability, non-B-DNA structure, human disease
Abstract: The transmission of genetic information relies on a coordinated network of cell cycle controls. Abnormalities in this network can result in genomic instability and lead to the transformation of normal cells into cancer cells. Chromosomal DNA replication is not only central to cellular division but also plays a crucial role in the maintenance of genomic integrity. DNA replication errors increase genetic instability, and may be a causative factor in diseases such as cancer and neuronal disorders. Replication in eukaryotes initiates from discrete genomic regions, termed origins, according to a strict, often tissue-specific, temporal program. The genetic program that controls activation of replication origins in mammalian cells has still not been elucidated. There is evidence that specification of replication sites and timing of replication are dynamic processes that are regulated by tissue-specific and developmental cues and that are responsive to epigenetic modifications. Here, we focus on the spatiotemporal regulation of DNA replication in the human genome. There is growing evidence that chromosome band patterns and epigenetic transformation of chromatin influence the timing of replication. On the basis of this evidence, we propose that the chromatin regions showing switches in replication timing from early to late in S phase are correlated with chromosome band boundaries. These chromatin regions generally display transitions in GC contents and include more non-B-form DNA structures than other genomic regions. We also examine here the effect of changes in replication timing on genomic stability and the possible role of replication timing in the etiology of diseases such as cancer. Replication timing assays are one of many promising techniques under investigation that may in future allow much earlier cancer detection than is possible today.
Export Options
About this article
Cite this article as:
Watanabe Yoshihisa and Maekawa Masato, Spatiotemporal Regulation of DNA Replication in the Human Genome and its Association with Genomic Instability and Disease, Current Medicinal Chemistry 2010; 17 (3) . https://dx.doi.org/10.2174/092986710790149756
DOI https://dx.doi.org/10.2174/092986710790149756 |
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 Advancement of Pyrazole Scaffold Based Neuroprotective Agents:
A Review
CNS & Neurological Disorders - Drug Targets Roles of p75NTR in Maintaining Brain Hemostasis and the Implications for p75NTR-targeted Therapies
Current Alzheimer Research The Identification and Characterization of Excitotoxic Nerve-endings in Alzheimer Disease
Current Alzheimer Research Oxidative RNA Damage and Neurodegeneration
Current Medicinal Chemistry Etiology of Neuroinflammatory Pathologies in Neurodegenerative Diseases: A Treatise
Current Psychopharmacology Davunetide: Peptide Therapeutic in Neurological Disorders
Current Medicinal Chemistry Dental Stem Cell Patents
Recent Patents on DNA & Gene Sequences Can Trehalose Prevent Neurodegeneration? Insights from Experimental Studies
Current Drug Targets Neuron Protection as a Therapeutic Target in Acute Ischemic Stroke
Current Topics in Medicinal Chemistry Glutamate in CNS Neurodegeneration and Cognition and its Regulation by GCPII Inhibition
Current Medicinal Chemistry Multifunctional Nanoparticles, Nanocages and Degradable Polymers as a Potential Novel Generation of Non-Invasive Molecular and Cellular Imaging Systems
Recent Patents on Nanotechnology Tetracyclines: Drugs with Huge Therapeutic Potential
Mini-Reviews in Medicinal Chemistry Protein Aggregation in Alzheimers Disease and Other Neoropathological Disorders
Current Alzheimer Research Potential for Stem Cells Therapy in Alzheimer’s Disease: Do Neurotrophic Factors Play Critical Role?
Current Alzheimer Research Does a Pro-Inflammatory Process Precede Alzheimers Disease and Mild Cognitive Impairment?
Current Alzheimer Research Histone Deacetylase (HDAC) Inhibitors - emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration
Current Neuropharmacology Humic Acids as Therapeutic Compounds in Lead Intoxication
Current Clinical Pharmacology Update on the Regulation of HIPK1, HIPK2 and HIPK3 Protein Kinases by microRNAs
MicroRNA Identifying S100B as a Biomarker and a Therapeutic Target For Brain Injury and Multiple Diseases
Current Medicinal Chemistry Use of Peripheral Blood Stem Cells in Tissue Engineering
Current Tissue Engineering (Discontinued)