Genome Stability

Genome Stability: From Virus to Human Application, Second Edition, a volume in the Translational Epigenetics series, explores how various species maintain genome stability and genome diversification in response to environmental factors. Here, across thirty-eight chapters, leading researchers provide a deep analysis of genome stability in DNA/RNA viruses, prokaryotes, single cell eukaryotes, lower multicellular eukaryotes, and mammals, examining how epigenetic factors contribute to genome stability and how these species pass memories of encounters to progeny. Topics also include major DNA repair mechanisms, the role of chromatin in genome stability, human diseases associated with genome instability, and genome stability in response to aging.

This second edition has been fully revised to address evolving research trends, including CRISPRs/Cas9 genome editing; conventional versus transgenic genome instability; breeding and genetic diseases associated with abnormal DNA repair; RNA and extrachromosomal DNA; cloning, stem cells, and embryo development; programmed genome instability; and conserved and divergent features of repair. This volume is an essential resource for geneticists, epigeneticists, and molecular biologists who are looking to gain a deeper understanding of this rapidly expanding　field, and can also be of great use to advanced students who are looking to gain additional expertise in genome stability.

Cover image
Title page
Table of Contents
Copyright
Contributors
Chapter 1: Genome stability: An evolutionary perspective
Abstract
1: Introduction
2: Evolution theories and the genome stability
3: The role of symbiosis in genome evolution
4: Fixation of a mutant allele in a population
5: Evolution of mutation rates
6: Genome instability: Is it random?
7: Genome evolution may be triggered by epigenetic modifications
8: Conclusion
Glossary
Part I: Genome instability of viruses
Chapter 2: Genetic instability of RNA viruses
Abstract
1: Introduction
2: Overview of RNA virus biology
3: Overview of RNA virus replication mechanisms
4: The viral polymerase as a source of error
5: Other viral determinants of mutation rate
6: Recombination
7: The effect of viral replication mechanisms on mutation accumulation
8: Effect of cellular factors on viral mutation rates
9: Mechanisms underlying genetic robustness in RNA viruses
10: Viruses as quasispecies
11: Genetic instability and virus intra-host adaptation
12: Genetic instability and virus inter-host adaptation
13: Genetic instability and virus emergence
14: Countermeasures based on virus genetic instability
15: Conclusion
Glossary
Chapter 3: Genome instability in DNA viruses
Abstract
1: Overview
2: Rates of spontaneous mutation and genetic diversity of DNA viruses
3: Mutator phenotypes produced by low-fidelity polymerases
4: DNA Coliphages and the MMR system
5: Interactions between DNA viruses and the eukaryotic DNA damage response
6: Diversity-generating retro-elements in bacteriophages
7: Recombination-driven genome instability in DNA viruses
8: APOBEC3 proteins and DNA virus genome instability
9: Conclusions and future directions
Glossary
Part II: Genome instability in bacteria and archaea
Chapter 4: Genome instability in bacteria and archaea: Strategies for maintaining genome stability
Abstract
1: Introduction
2: Responses to DNA damage
3: DNA repair pathways
4: Restriction-modification systems: Protecting the genome from invaders
5: Conclusion
Glossary
Chapter 5: Genome instability in bacteria: Causes and consequences
Abstract
1: Introduction
2: Effects of stress responses on genome instability
3: Genome instability due to stable mutator genotypes
4: Genome instability due to homologous and illegitimate recombination
5: Genome instability due to specialized genetic elements
6: Genome instability due to genetic exchange
7: Conclusion
Glossary
Chapter 6: CRISPR – Bacterial immune system
Abstract
1: Introduction
2: History of the CRISPR/Cas discovery
3: Structure of the CRISPR loci
4: CRISPR/Cas classification
5: Composition of the CRISPR/Cas systems
6: Molecular machinery of CRISPR/Cas systems
7: CRISPR/Cas systems at work
8: Other roles of the CRISPR/Cas systems
9: Origins and evolution of the CRISPR/Cas systems
10: Conclusion
Glossary
Part III: Genome stability of unicellular eukaryotes
Chapter 7: From micronucleus to macronucleus: Programmed DNA rearrangement in ciliates is regulated by non-coding RNA molecules
Abstract
1: Introduction
2: The sexual life circle of ciliates
3: Organization of the micro- and macronuclear genomes
4: Epigenetic regulation of macronuclear development in Tetrahymena
5: Epigenetic regulation of macronuclear development in stichotrichous ciliates
6: New advances in ciliates research
7: Conclusion
Glossary
Chapter 8: Homologous recombination and nonhomologous end-joining repair in yeast
Abstract
1: Introduction
2: Homologous recombination models
3: Common HR steps
4: Non-homologous end joining
5: The role of epigenetics in double-strand break repair
6: Conclusion
Glossary
Part IV: Genome stability in multicellular eukaryotes
Chapter 9: Meiotic and mitotic recombination: First in flies
Abstract
1: Introduction
2: Mitotic recombination
3: Meiotic recombination
4: Drosophila: The next 100 years
Glossary
Chapter 10: Genome stability in Drosophila: Mismatch repair and genome stability
Abstract
1: Introduction
2: MMR activity in Drosophila
3: MMR genes in Drosophila
4: MMR and microsatellite instability (MSI)
5: The role of MMR on meiotic recombination
6: MMR and somatic cell mutations
7: Conclusion
Glossary
Chapter 11: Genome stability in Caenorhabditis elegans☆
Abstract
1: Introduction
2: The Caenorhabditis elegans model
3: Powerful genetic tools to explore DDR dynamics
4: Genotoxic agents for DNA-damage induction
5: Methods for DNA-damage detection
6: Excision repair
7: Mismatch repair
8: Double-strand break repair in C. elegans
9: DNA-damage checkpoints
10: Concluding remarks
Glossary
Chapter 12: Plant genome stability—General mechanisms
Abstract
1: Introduction
2: The DNA-damaging agents
3: Sensing the DNA damage
4: Chromatin architecture and DNA repair
5: Photoreactivation
6: Base excision repair
7: Nucleotide excision repair (NER)
8: Mismatch repair (MMR)
9: DNA double-strand break repair (DSBR)
10: DNA repair in organelles
11: Future perspective
Glossary
Chapter 13: Genetic engineering in plants using CRISPRs
Abstract
1: Introduction
2: Gene editing using CRISPR/Cas9
3: Base editors
4: Prime editing
5: CRISPR-mediated activation (CRISPRa) and CRISPR interference (CRISPRi)
6: CRISPR-mediated directed evolution (CDE)
7: Gene editing in plants using novel Cas variants
8: Alternative and future applications of the CRISPR-based technology
9: Conclusions
Glossary
Part V: Genome stability in mammals
Chapter 14: Cell cycle control and DNA-damage signaling in mammals
Abstract
1: Introduction
2: Cell cycle progression in mammalian cells
3: DNA-damage signaling and repair in mammals
4: Checkpoint control: DNA-damage signaling and the mammalian cell cycle
5: Conclusion
Glossary
Chapter 15: The role of p53/p21/p16 in DNA damage signaling and DNA repair
Abstract
1: Introduction
2: The p53 tumor suppressor protein
3: The p21 protein: An oncogene, a tumor suppressor, or both?
4: The p16INK4A tumor suppressor protein
5: Conclusion
Glossary
Chapter 16: Roles of RAD18 in DNA replication and post-replication repair (PRR)
Abstract
1: Introduction: The DDR, DNA damage tolerance and DNA damage avoidance mechanisms
2: Identification of RAD18-RAD6 as a mediator of DNA damage tolerance
3: RAD18-mediated PCNA mono-ubiquitination and the TLS polymerase switch
4: RAD18 structure, activation, and coordination with the DDR
5: DNA replication-independent RAD18 activation and TLS
6: RAD18 functions in error-free PRR via template switching
7: TLS and TS-independent roles of RAD18 in genome maintenance
8: Physiological roles of RAD18
9: Conclusions and perspectives
Glossary
Chapter 17: Base excision repair and nucleotide excision repair
Abstract
Acknowledgment
1: General overview and historical perspectives of two DNA excision repair pathways, BER and NER
2: Mammalian BER
3: Mammalian NER
4: Biological implications beyond DNA damage and repair
5: Interplay between NER and BER: The key role of the DNA damage response for prevention of cellular degeneration
6: Concluding remarks
Glossary
Chapter 18: DNA mismatch repair in mammals
Abstract
Acknowledgments
1: Introduction and brief history
2: Post-replication mismatch repair
3: Mismatch repair and the DNA damage response
4: Regulation of MMR
5: Mismatch repair disorders and colorectal cancer
6: Role of mismatch repair in antibody diversity
7: Role of mismatch repair in repeat expansion disorders
8: Role of MMR in homologous recombination
9: Conclusions
Glossary
Chapter 19: Repair of double-strand breaks by nonhomologous end joining; Its components and their function
Abstract
1: Introduction
2: Classical NHEJ
3: Alternative NHEJ
4: End-processing
5: Conclusions
Glossary
Chapter 20: Homologous recombination in mammalian cells: From molecular mechanisms to pathology
Abstract
1: Introduction
2: Roles of HR in the equilibrium of genetic stability versus diversity
3: Molecular mechanisms and regulation of HR
4: Roles of HR in replication fork reactivation and DSB repair
5: HR and transcribed sequences
6: Meiosis
7: Dark side of HR: Promotion of genome instability
8: Protection against excessive HR
9: Homologous recombination, genome stability, and cancer
10: HR in genomic molecular evolution
11: Concluding remarks
Glossary
Chapter 21: Telomere maintenance and genome stability
Abstract
Acknowledgements
1: Introduction
2: Telomere length and telomerase regulation
3: Architecture and function of telomerase
4: Telomeric DNA structure
5: Telomere-interacting complexes
6: Telomere-associated diseases
7: Telomeres as a DNA damage prevention system
8: Cancer treatments targeting telomeres and telomerase
9: Conclusions and closing remarks
Glossary
Chapter 22: Chromatin, nuclear organization and genome stability in mammals
Abstract
1: Introduction
2: Histones
3: Histone variants
4: Histone modifications
5: Nucleosomes and the 30-nm fiber
6: Higher order structures
7: Chromatin remodelers
8: Access, repair, restore
9: Nuclear organization of chromatin
10: Chromosome territories
11: Transcription and replication in the nucleus
12: Conclusions
Glossary
Chapter 23: Role of DNA methylation in genome stability
Abstract
1: Introduction to the cellular functions of DNA methylation
2: Multi-faceted regulation of genome stability by DNA methylation
3: Conclusions and future direction
Glossary
Chapter 24: Non-coding RNAs in genome integrity
Abstract
1: Introduction
2: Targeting bacteriophage genomes by CRISPRs/Cas9
3: DNA elimination in ciliates
4: Telomerase RNA and telomere length
5: Role of micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the regulation of DNA repair and genome stability
6: The role of Piwi-interacting RNA (piRNA) in the maintenance of genome stability in the germline
7: The role of small interfering RNAs (siRNAs) in the maintenance of genome stability
8: Conclusion
Glossary
Part VI: Human diseases associated with genome instability
Chapter 25: Human diseases associated with genome instability
Abstract
1: Introduction
2: Rare genetic diseases associated with DNA repair
Glossary
Chapter 26: Cancer and genomic instability
Abstract
1: Introduction
2: DNA repair pathways
3: Genomic instability in hereditary cancer
4: Genomic instability in sporadic cancers
5: Triggering excessive genomic instability by targeting DNA repair pathways as a strategy for cancer therapy
6: Conclusion
Glossary
Chapter 27: Epigenetic regulation of the cell cycle & DNA-repair in cancer
Abstract
1: Contractor: The chromatin chronicles
2: Bookmarker: Conserving cell identity through cell division
3: Booster: Regulating cell-specific enhancers
4: Engineering for all weather: Controlling DNA repair activity in normal and cancer cells
5: Conclusion and outlook
Chapter 28: Genomic instability and aging: Causes and consequences
Abstract
Acknowledgments
1: Introduction
2: Age-related accumulation of DNA damage and genomic instability
3: Causes of age-dependent accumulation of genomic instability
4: Genomic regions with various susceptibility to genomic instability
5: Role of genomic instability in aging?
6: Conclusion
Glossary
Chapter 29: The DNA damage response and neurodegeneration: Highlighting the role of the nucleolus in genome (in)stability
Abstract
1: Introduction
2: Nucleolus as a sensor of neuronal DNA damage
3: Neurodegeneration-associated instability of rDNA
4: Concluding remarks
Glossary
Part VII: Effect of environment on genome stability
Chapter 30: Diet and nutrition
Abstract
1: Introduction
2: Dietary causes of genomic instability
3: Dietary protection against genomic instability
4: The significance of genetic polymorphisms
5: Conclusions
Glossary
Chapter 31: Chemical carcinogens and their effect on genome and epigenome stability
Abstract
1: Introduction
2: Epigenetic regulators
3: Effects of environmental toxicants
4: Tamoxifen effects
5: Other toxicants and chemicals
6: Conclusions
Glossary
Chapter 32: Modern sources of environmental ionizing radiation exposure and associated health consequences
Abstract
1: Introduction
2: The molecular effects of ionizing radiation in cells
3: Radiation dosage and linear energy transfer (LET)
4: Nuclear military attacks and civilian nuclear disasters
5: Aerospace travel and cosmic ray exposure
6: Medical radiation and photon radiation exposure
7: Radon gas and alpha particle IR exposure
8: Conclusion
Glossary
Part VIII: Bystander and transgenerational effects: Epigenetic perspective
Chapter 33: Sins of fathers through a scientific lens: Transgenerational effects
Abstract
1: Introduction
2: Radiation-induced genome instability
3: Mechanisms of transgenerational effects: Epigenetic changes
4: Transgenerational effects caused by other mutagens
5: Conclusions and outlook
Glossary
Chapter 34: Radiation and chemical induced genomic instability as a driver for environmental evolution
Abstract
1: General introduction
2: Mechanisms and signals
3: Evidence and insights from chemical ecology
4: Transmission of information between organisms post irradiation
5: Role of genomic instability and bystander effects
6: DNA and DAMPs
7: Discussion
8: Conclusion
Glossary
Chapter 35: Transgenerational genome instability in plants
Abstract
1: Introduction
2: Genome stability may depend upon the choice of the DSB DNA repair pathway
3: Epigenetic regulation of plant genome stability
4: Transgenerational responses
5: Possible mechanisms involved in the regulation of transgenerational inheritance of stress memory
6: Concluding remarks
Glossary
Chapter 36: Methods for the detection of DNA damage
Abstract
Acknowledgments
1: Introduction
2: The detection of DSBs in cultivated mammalian cells and tissues
3: γH2AX in biodosimetry and clinical assays
4: Comet assay
5: Methods for studying DNA repair after UV
6: Conclusions
Chapter 37: Conserved and divergent features of DNA repair. Future perspectives in genome stability research
Abstract
1: An overview and comparison of DNA repair pathways in different organisms
2: Recent advances and future directions in DNA repair
3: Future directions in research on DNA repair, genome stability, and cancer
4: Future perspectives in DNA editing technologies
Glossary
Chapter 38: Off-target effects in genome editing
Abstract
1: Types of nucleases used for genome editing
2: The potential for off-target effects
3: Methods for the prediction and detection of off-target events
4: Strategies for reducing off-target effects
5: Conclusion
Glossary
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Genome Stability

From Virus to Human Application

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Igor Kovalchuk

Olga Kovalchuk

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