Genome Stability. From Virus to Human Application

659 Pages·2016·31.352 MB·English

by  Igor Kovalchuk, Olga Kovalchuk

Translational Epigenetics Series
Trygve O. Tollefsbol, Series Editor
Transgenerational Epigenetics
Edited by Trygve O. Tollefsbol, 2014
Personalized Epigenetics
Edited by Trygve O. Tollefsbol, 2015
Epigenetic Technological Applications
Edited by Y. George Zheng, 2015
Epigenetic Cancer Therapy
Edited by Steven G. Gray, 2015
DNA Methylation and Complex Human Disease
By Michel Neidhart, 2015
Epigenomics in Health and Disease
Edited by Mario F. Fraga and Agustin F. Fernández, 2015
DNA Biomarkers and Diagnostics
Edited by José Luis García-Giménez, 2015
Drug Discovery in Cancer Epigenetics
Edited by Gerda Egger and Paola Arimondo, 2015
Medical Epigenetics
Edited by Trygve O. Tollefsbol, 2016
Chromatin Signaling
Edited by Olivier Binda and Martin Fernandez-Zapico, 2016
Genome Stability
From Virus to Human Application
Edited by
Igor Kovalchuk
Olga Kovalchuk
University of Lethbridge, Lethbridge, AB, Canada
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List of Contributors
A. Anikin University of Calgary, Calgary, AB, Canada A.A. Goodarzi University of Calgary, Calgary, AB,
Canada
J.N. Barr University of Leeds, Leeds, United Kingdom
R. Gundogdu University College London, London, United
A. Bilichak Agriculture and Agri-Food Canada,
Kingdom
Lethbridge, AB, Canada
T. Hatkevich University of North Carolina, Chapel Hill,
D. Bonatto Federal University of Rio Grande do Sul, Porto
NC, United States
Alegre, Brazil
A. Hergovich University College London, London, United
L. Boteva The University of Edinburgh, Edinburgh, United
Kingdom
Kingdom
W. Hernandez-Sanchez Case Western Reserve University,
Y. Cheng University of British Columbia, Vancouver, BC,
Cleveland, OH, United States
Canada; Xiamen University, Xiamen, P.R. China
M. Hetman University of Louisville, Louisville, KY,
J. Cobb University of Calgary, Calgary, AB, Canada
United States
J. de Faria Poloni Federal University of Rio Grande do
J.K. Holsclaw University of North Carolina, Chapel Hill,
Sul, Porto Alegre, Brazil
NC, United States
F. Eudes Agriculture and Agri-Food Canada, Lethbridge,
P. Hsieh National Institutes of Health, Bethesda, MD,
AB, Canada
United States
R. Fearns Boston University School of Medicine, Boston,
T.C. Humphrey University of Oxford, Oxford, United
MA, United States
Kingdom
B.C. Feltes Federal University of Rio Grande do Sul, Porto
T. Izumi University of Kentucky, Lexington, KY, United
Alegre, Brazil
States
L.R. Ferguson University of Auckland, Auckland, New
R.E. Jones University of Oxford, Oxford, United Kingdom
Zealand
F. Jönsson University of Witten/Herdecke, Witten,
D.V. Firsanov Institute of Cytology of the Russian
Germany
Academy of Sciences, Saint-Petersburg, Russia;
Nikiforov Russian Center of Emergency and Radiation I. Kovalchuk University of Lethbridge, Lethbridge, AB,
Medicine of the EMERCOM of Russia, Saint- Canada
Petersburg, Russia
O. Kovalchuk University of Lethbridge, Lethbridge, AB,
Y. Gao University of North Carolina at Chapel Hill, Chapel Canada
Hill, NC, United States
Y. Kulaberoglu University College London, London,
C. Gelot Université Paris-Saclay, Villejuif, France United Kingdom
N. Gilbert The University of Edinburgh, Edinburgh, T. Le-Guen Université Paris-Saclay, Villejuif, France
United Kingdom
A.F.C. Lopes University of Cologne, Cologne, Germany
R.M. Golsteyn University of Lethbridge, Lethbridge, AB,
B.S. Lopez Université Paris-Saclay, Villejuif, France
Canada
I. Mellon University of Kentucky, Lexington, KY, United
A. Golubov University of Lethbridge, Lethbridge, AB,
States
Canada
M. Merrifield University of Lethbridge, Lethbridge, AB,
V. Gomez University College London, London, United
Canada
Kingdom
xvii
xviii List of Contributors
J.-E. Messling University of Cologne, Cologne, Germany J. Sekelsky University of North Carolina, Chapel Hill, NC,
United States
V.M. Mikhailov Institute of Cytology of the Russian
Academy of Sciences, Saint-Petersburg, Russia C. Seymour McMaster University, Hamilton, ON, Canada
K.N. Miyamoto Federal University of Rio Grande do Sul, C. Sidler ETH Zürich, Zürich, Switzerland
Porto Alegre, Brazil
L.V. Solovjeva Institute of Cytology of the Russian
P. Moskwa Medical University of Greifswald, Greifswald, Academy of Sciences, Saint-Petersburg, Russia
Mecklenburg-Vorpommern, Germany
M.P. Svetlova Institute of Cytology of the Russian
C. Mothersill McMaster University, Hamilton, ON, Academy of Sciences, Saint-Petersburg, Russia
Canada
L.H. Swift University of Lethbridge, Lethbridge, AB,
E. Mutter-Rottmayer University of North Carolina at Canada
Chapel Hill, Chapel Hill, NC, United States
S. Tateishi Kumamoto University, Kumamoto, Japan
T. Negishi Okayama University, Okayama, Japan
D.J. Taylor Case Western Reserve University, Cleveland,
D.D. Pearson University of Calgary, Calgary, AB, Canada OH, United States
M. Pereira-Gómez Universitat de València, Paterna, Spain C. Vaziri University of North Carolina at Chapel Hill,
Chapel Hill, NC, United States
S. Ragu Université Paris-Saclay, Villejuif, France
B. Wang University of Lethbridge, Lethbridge, AB,
M. Renaud-Young University of Calgary, Calgary, AB,
Canada
Canada
W. Wei Massachusetts General Hospital Cancer Center,
K. Riabowol University of Calgary, Calgary, AB, Canada
Boston, MA, United States
M. Rieckher University of Cologne, Cologne, Germany
A.B. Williams University of Cologne, Cologne, Germany
J. Risso Universitat de València, Paterna, Spain
M. Xu Case Western Reserve University, Cleveland, OH,
K.D. Robertson Mayo Clinic, Rochester, MN, United
United States
States
M. Yang National Institutes of Health, Bethesda, MD,
R. Sanjuán Universitat de València, Paterna, Spain
United States
B. Schumacher University of Cologne, Cologne, Germany
D. Zhou Mayo Clinic, Rochester, MN, United States
Introduction
We have made our best efforts to collect chapters covering research on DNA repair and genome stability/instability in
various species belonging to all domains of life. Moreover, we thought it would be very beneficial to give an epigenetics
perspective to understanding of the regulation of DNA repair and genome stability. Therefore, several chapters discuss the
role of the environment in DNA repair and genome stability. We also attempted to summarize genome changes during the
evolution of new species, with an emphasis on randomness and nonrandomness of changes in various species. Finally, we
have attempted to compare DNA-repair pathways in different organisms and to summarize what can be potentially done in
the future to know more about DNA repair and genome stability.
The opening chapter (Chapter 1) of this book is “Genome stability: an evolutionary perspective” by Igor Kovalchuk. In
this chapter, he discusses various aspects of genome evolution, by presenting the case of both Lamarckian and Darwinian
models of evolution, describing the role of the environment in evolution and in particular in genome evolution, and explain-
ing how the genetic and epigenetic components of DNA repair and genome stability have evolved. The chapter also touches
upon some interesting controversies over the randomness or nonrandomness of changes in the genome, as well as the rate
of DNA repair in various genomic regions in the same or different species.
In the next several chapters, we discuss the aspects of DNA repair and genome stability across all domains of life.
Specifically, the chapters by John Barr and Rachel Fearns, Rafael Sanjuán, Marianoel Pereira-Gómez, and Jennifer Risso
describe DNA-repair mechanisms and the aspects of genome instability in RNA and DNA viruses, respectively. In the
chapter covering genome stability in RNA viruses (Chapter 2), Barr and Fearns describe how RNA viruses are able to
withstand challenge with antiviral drugs and cause epidemics in previously exposed human populations. They also describe
an extraordinary degree of genetic heterogeneity in RNA viruses; RNA viruses exist not as single genotypes but as swarms
of related variants, and this genomic diversity is an essential feature of their biology. It appears that RNA viruses have a
variety of mechanisms that act in combination to determine their genetic heterogeneity, such as polymerase fidelity, error-
mitigation mechanisms, genomic recombination, and different modes of genome replication. Finally, Barr and Fearns
present the evidence that some RNA viruses operate close to a threshold where the polymerase error rate has evolved to
maximize the availability of the possible sequence space, while avoiding the accumulation of lethal deleterious mutations.
Describing genome stability of DNA viruses (Chapter 3), Sanjuán and colleagues show that DNA viruses can exhibit
rapid sequence changes that are often found in loci involved in dynamic host–virus interactions. In particular, they describe
that DNA viruses are capable of promoting genomic instability of certain specific genes, thus boosting the diversity where
it is needed. Among specific mechanisms maintaining the viral diversity are diversity-generating retro-elements, a recom-
bination-driven gene amplification, and DNA editing by host-encoded deaminases.
The second section of the book describes DNA repair and genome instability in prokaryotes. This section includes
chapters by Ashley Williams and colleagues in which they compare genome stability of bacteria and archaea (Chapter 4),
and show the role of the environment in bacterial mutagenesis (Chapter 5). Jan-Erik Messling and Ashley B. Williams dem-
onstrate that through a careful regulation, prokaryotic cells employ the complex and sophisticated pathways that maintain a
balance between genome stability and instability to allow not only self-preservation in future generations but also a genetic
innovation for continued adaptation and evolution. They discuss the basic mechanisms that bacteria and archaea use to limit
genome instability and also compare different approaches used by these two domains of life to face assaults by both endog-
enous and exogenous forces. In Chapter 5, Ashley Williams discusses various sources of genome instability in bacteria,
including stress responses, mutator genotypes, recombination, specialized genetic sequences, and mobile genetic elements.
They also show the consequences of these different pathways, with a specific focus on those ones that impact pathogens and
their interactions with their hosts. In Chapter 6, Adnrey Golubov describes an ancient bacterial immune system—CRISPR/
Cas9. He discusses the history of research on CRISPR/Cas9, the genetic structure of this system and its molecular mecha-
nisms of action and regulation. The discovery of CRISPRs and a path to its application in genetic engineering is an example
of a rare breakthrough that revolutionizes science and technology. It is not surprising that in 2015, the CRISPRs technology
has been named one of the breakthrough technologies of the year by Science magazine.
xix
xx Introduction
The third section of this book covers genome stability of unicellular eukaryotes by presenting two chapters which address
genome stability in ciliates by Franziska Jönsson (Chapter 7) and genome stability in yeasts by Rebecca Jones and Timothy
Humphrey (Chapter 8). Ciliates are unique organisms as far as genome stability is concerned because they involve massive
developmentally regulated changes in the genome structure driven by noncoding RNAs (ncRNAs). Franziska Jönsson com-
pares the macronuclear development of two distantly related ciliate classes to show how the nuclear organization reflects
different types of adaptation and regulation mechanisms exhibiting the power of ncRNAs in genome evolution.
In Chapter 8, Rebecca Jones and Timothy Humphrey describe the details of double-strand break (DSB) repair pathways
in yeast.
Section 4 of the book focuses on DNA repair and genome stability in multicellular eukaryotes, excluding mammals.
In Chapter 9, Julie Korda Holsclaw, Talia Hatkevich, and Jeff Sekelsky describe the major mitotic DSB-repair pathways,
homologous recombination (HR) repair, and end joining in Drosophila. Specifically, they discuss the key regulatory
mechanisms of meiotic recombination that promote repair of meiotic DSBs in the form of crossovers and present a novel
model recently introduced for meiotic recombination in Drosophila. Research in Drosophila has been complemented by
Chapter 10 presented by Tomoe Negishi who describes the role of mismatch repair (MMR) activities in genome stabil-
ity of Drosophila, reviewing the role of MMR in meiotic recombination, mitotic DNA replication, and the induction of
mutations.
In Chapter 11, Matthias Rieckher, Amanda Franqueira Lopes, and Björn Schumacher provide an overview of DNA
repair and DNA-damage response mechanisms in Caenorhabditis elegans and various methodologies that have been
employed to gain an insight into metazoan genome stability.
Chapters 12 and 13 cover research in plants. In Chapter 12, Andriy Bilichak provides a review of the most important
DNA-repair pathways in plants that work together during plant development for an efficient maintenance of genome sta-
bility and plant survival, whereas in Chapter 13, Andriy Bilichak and Francois Eudes describe the use of three modern
genome-editing technologies, zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly
interspaced short palindromic repeats/Cas9, that are used for permanent modifications of plants. The authors present an
overview of the discovery of each of the technologies, their benefits, limitations, and their potential effectiveness for the
future development of genetic engineering in plants.
Section 5 of the book is the largest one covering details of various DNA-repair pathways utilized by mammals to repair
DNA. The section begins with Chapter 14 by Valenti Gomez and Alexander Hergovich focusing on the regulation of the
mammalian cell cycle in the context of DNA-damage signaling and DNA damage–repair mechanisms. The authors also
discuss some molecular aspects in the context of diseases. In Chapter 15, Yavuz Kulaberoglu, Ramazan Gundogdu, and
Alexander Hergovich provide an overview of an important role of p53, p21, and p16 in cell-intrinsic checkpoints as well as
signaling and repair responses to prevent genome instability. They also discuss the significance of these tumor suppressors
in the context of cancer and DNA-damaging therapies designed to specifically target tumor cells.
Further details of DNA repair and genome stability in mammals are presented by Cyrus Vaziri, Satoshi Tateishi, Elizabeth
Mutter-Rottmayer, and Yanzhe Gao in Chapter 16 that describes the role of RAD18 in DNA replication and post-replication
repair (PRR). The authors review the mechanisms of RAD18 activation in response to DNA damage, its participation in trans-
lesion DNA synthesis and template switching, and the basis for the integration of RAD18 activity with other elements of the
DNA-damage response and the cell cycle. The authors also discuss the potential impact of RAD18 on genome stability and
tumorigenesis.
In Chapter 17, Tadahide Izumi and Isabel Mellon introduce the history and concepts of DNA-excision repair, discuss
types of DNA damage processed by base-excision repair (BER) and nucleotide-excision repair (NER), and describe the
repair mechanisms. The authors present a recent evidence indicating that DNA-damage and excision-repair proteins are key
signal transducers and play critical roles in DNA-damage responses and communications between nuclei and mitochondria.
In Chapter 18, Mingzhang Yang and Peggy Hsieh summarize current knowledge of the mechanism of MMR in mam-
malian cells, its role in DNA-damage signaling, and its contribution to the maintenance of genome stability and tumor
suppression.
In Chapter 19, Patryk Moskwa introduces nonhomologous end joining (NHEJ) repair pathways of DSBs and their com-
ponents in mammals. He covers the details of their function, structure, binding partners, and possible regulations.
In Chapter 20, Camille Gelot, Tangui Le-Guen, Sandrine Ragu, and S. Bernard summarize different molecular mecha-
nisms of HR in mammals. They discuss the role of HR in DNA DSB repair, the reactivation of arrested replication forks,
and their consequences (radiation sensitivity, meiosis, and the application in genome manipulation). The authors propose a
model for the choice of the DSB-repair pathway that functions in two steps: ssDNA resection versus the canonical NHEJ
pathway and alternative end-joining pathway versus HR on resected DNA. Finally, the authors present the role of HR in the
molecular evolution of multigene families in the process of concerted evolution.
Introduction xxi
In Chapter 21, the role of telomere maintenance in genome stability is introduced by Wilnelly Hernandez-Sanchez,
Mengyuan Xu, and Derek J. Taylor. The authors describe recent advances that suggest the involvement of dysfunctional
telomeres or the improper regulation of telomerase activity in the development of a host of human diseases that include
premature aging syndromes, bone marrow failures, and cancer.
In Chapter 22, Lucy H. Swift and Roy M. Golsteyn describe the relationship between checkpoint adaptation and mitotic
catastrophe in cancer cells. They review factors that contribute to checkpoint adaptation, such as the cell cycle, checkpoints,
mitotic catastrophe, and cell death, and describe their relationship to genome instability. The authors suggest that distin-
guishing checkpoint adaptation from apoptosis will aid in the study of how genome instability is generated and amplified
in cancer cells.
The following three chapters of this section introduce the role of epigenetic components in the regulation of genome
stability. Chapter 23 by Lora Boteva and Nick Gilbert describe an indispensable role of the chromatin structure and nuclear
organization in DNA repair and the maintenance of genome stability. The authors present a modern view in which genome
stability aims to integrate the influence of fundamental cellular processes such as transcription and replication with the
chromatin context in order to get a better understanding of the processes that shaped the human genome. In Chapter 24,
Dan Zhou and Keith Robertson describe the role of DNA methylation in the maintenance of genome stability. The authors
describe how DNA methylation and DNA methyltransferases assist in recognizing mismatches, while also contributing to
genome stability by regulating MMR gene transcription. The authors show how intensive DNA methylation at heterochro-
matin repeats stabilizes such domains from their translocation and undesired spreading, ensuring the appropriate functions
of centromeres and telomeres as well as the genetic integrity. Finally, in Chapter 25, Igor Kovalchuk explains how ncRNAs
play direct and indirect roles in the regulation of genome stability.
Section 6 covers human genetic diseases and conditions associated with genome instability. In Chapter 26, Bruno
César Feltes, Joice de FariaPoloni, Kendi Nishino Miyamoto, and DiegoBonatto describe human diseases associated with
genome instability. The authors review the repair machineries underlying rare genetic diseases and different types of cancer.
Chapters 27 and 28 present genome instability in cancer. Specifically, in Chapter 27, Wei Wei, Yabin Cheng, and Bo Wang
provide a comprehensive coverage of various DNA-repair pathways and their contribution to almost all types of human
malignancies. In this chapter, they describe the current understanding of defects in DNA-repair pathways in the develop-
ment of cancer as well as DNA-repair pathway targeting as a potential strategy for cancer therapy. In Chapter 28, Margaret
Renaud-Young, Karl Riabowol, and Jennifer Cobb describe the epigenetic regulation of the cell cycle and DNA repair in
cancer. Since the ability of proteins in different repair pathways to find and repair lesions is critical in the maintenance of
genome stability and prevention of cancer, work in the chromatin field is particularly important to understand the chromatin
dynamics during DNA-damage recognition and repair. The authors summarize the factors regulating chromatin changes
that are critical in mediating the repair of DNA damage.
Chapter 29 by Corinne Sidler introduces us to the world of aging and the role that genome instability plays in this
process. The author presents several lines of evidence showing that the accumulation of unrepaired DNA damage and the
resulting genomic instability play a central role in promoting aging.
In Chapter 30, Michal Hetman describes the function of the nucleolus in the DNA-damage response and the genomic
(in)stability in the nervous system. In this chapter, the mechanisms and potential consequences of nucleolar involvement in
the genomic instability are discussed in detail.
Section 7 focuses on the effects of the environment on genome stability. In Chapter 31, Lynnette Ferguson describes the
association between variations in the diet, changes in the level of free radicals, and DNA damage. The author discusses how
diets enriched with various nutrients and phytochemicals may provide DNA protection. Furthermore, the author discusses
how polymorphisms in genes for nutrient uptake, metabolism, and excretion can determine the optimal dietary intake for
an individual. In Chapter 32, Olga Kovalchuk describes the role of chemicals and chemical mutagenesis in DNA repair and
genome instability. In Chapter 33, Aaron Goodarzi, Alexander Anikin, and Dustin Pearson describe how the ionizing radia-
tion (IR) from environmental sources affects human health. They review the primary sources of human IR exposure, includ-
ing a nuclear attack, civilian nuclear disasters, aerospace travel, medical radiation (radiotherapy and computed tomography
imaging), and radon gas inhalation, and their health consequences.
Section 8 covers epigenetic perspective of bystander and transgenerational effects. In Chapter 34, Matt Merrifield and
Olga Kovalchuk introduce the concept of transgenerational response in animals and describe how this phenomenon is
controlled by epigenetic components. They specifically focus on the effect of IR, describing direct and indirect effects and
introducing the concept of bystander and nontargeted effects of IR. In Chapter 35, Carmel Mothersill and Colin Seymour
discuss whether low doses of radiation are harmful or good. The authors present some of the reasons for the controversy
and mistrust. They propose that we as humans need to accept uncertainty; they also suggest some approaches to developing
protection frameworks which might be more fruitful.
xxii Introduction
In Chapter 36, Igor Kovalchuk introduces the concept of transgenerational response in plants. The author describes
changes that occur in response to stress at the level of genome stability and epigenome regulation and discusses the role of
transgenerational response to stress in plants for the regulation of genome stability.
Chapter 37 by Firsanov, Solovjeva, Mikhailov, and Svetlova presents various methods that can be used to analyze DNA
damage and changes in genome stability. They pay a special attention to immunological methods of monitoring DNA dam-
age and repair in single cells.
Finally, Chapter 38 by Igor Kovalchuk presents a logical summary of the book “Conserved and divergent features of
DNA repair. Future perspectives in genome-instability research.” In this chapter, the author describes differences in DNA
repair among bacteria, archaea, and eukarya and suggests potential future directions in DNA-damage repair and genome-
stability research.
Igor Kovalchuk
Olga Kovalchuk
Chapter 1
Genome Stability: An Evolutionary
Perspective
I. Kovalchuk
University of Lethbridge, Lethbridge, AB, Canada
Chapter Outline
1. Introduction 1 5. Evolution of Mutation Rates 7
2. Evolution Theories and My Reflection on Them 2 5.1 Evolution of Somatic Mutation Rates 9
3. The Role of Symbiosis in Genome Evolution 3 6. Genome Instability: Is It Random? 11
3.1 Changes in the Structure of the Organellar Genome Over 6.1 A Bias in Mutations in Different Genomic Regions 12
Time 4 7. Genome Evolution May Start From Changes at the Level
3.2 Mutation Rates in Organellar Genomes and Adaptive of DNA Methylation or Chromatin Modification 13
Evolution 4 8. Conclusion 15
3.3 Symbiotic Interactions Between Viruses, Prokaryotes, and Glossary 15
Eukaryotes: The Role of Transposable Elements 5 List of Abbreviations 16
4. Fixation of a Mutant Allele in a Population 6 References 16
1. INTRODUCTION
Genome stability is a feature of every organism to preserve and faithfully transmit the genetic material from generation to
generation or from one somatic cell to another. This includes an error-free replication of genetic material (DNA or RNA)
and the repair of replication mistakes or damaged DNA/RNA (see the corresponding chapters in this book). In contrast,
genome instability covers a broad range of topics referring to an increased rate of DNA damage and the associated muta-
tions, the role of potential direct and indirect mutagens, the role of external and internal factors contributing or mitigating
such instability, and so on.
In this chapter, we discuss genome stability/instability from the perspective of evolution, and specifically genome
evolution. Genome evolution refers to changes in the genome structure or genome size over time. Usually, such changes
are changes in the DNA (RNA) sequence that are passed on to the progeny and the accumulation/fixation of such genetic
variants or their rejection in a population. Genome evolution is normally discussed in the context of evolution of new
species, and thus it is closely associated with the appearance of new traits, new phenotypical and morphological features,
and so on.
Considering that new traits and phenotypes may develop due to epigenetic changes, it is plausible to think that genome
evolution in part also involves changes in genome structure due to epigenetic modifications. In contrast to genetic changes
that include mutations in the DNA sequence, epigenetic changes involve heritable but potentially reversible changes in gene
expression due to changes in DNA methylation and histone modifications, among others.
Hence, how does the genome actually evolve? What are driving forces in genome evolution? Does evolution have the
spontaneous and random nature? Is it actually directed and driven by changes in the external and internal environment?
In the following, we contrast Darwin’s and Lamarck’s views on evolution and discuss the mechanisms that impact rate of
evolution and the crucial role of the environment, especially as far as evolution of genome is concerned.
Genome Stability. http://dx.doi.org/10.1016/B978-0-12-803309-8.00001-X
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