Genome Stability

Genome Stability

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 ...

Author: Igor Kovalchuk

Publisher: Academic Press

ISBN: 9780323856805

Category: Science

Page: 760

View: 564

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. A deep analysis of genome stability research from various kingdoms, including epigenetics and transgenerational effects Provides comprehensive coverage of mechanisms utilized by different organisms to maintain genomic stability Contains applications of genome instability research and outcomes for human disease Features all-new chapters on evolving areas of genome stability research, including CRISPRs/Cas9 genome editing, RNA and extrachromosomal DNA, programmed genome instability, and conserved and divergent features of repair
Categories: Science

Genome Instability

Genome Instability

This volume presents forty-two methods and protocols to analyze diverse aspects of genome instability.

Author: Marco Muzi-Falconi

Publisher: Humana Press

ISBN: 1493973053

Category: Medical

Page: 663

View: 234

This volume presents forty-two methods and protocols to analyze diverse aspects of genome instability. Chapters detail mutagenesis and repair, methods to quantify and analyze the properties of DNA double-strand breaks, profile replication, replication proteins strand-specifically, genome instability, fluorescence microscopic techniques, and genomic and proteomic approaches. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Genome Instability: Methods and Protocols aims to provide a comprehensive resource for the discovery and analysis of the proteins and pathways that are critical for stable maintenance of the genome.
Categories: Medical

Genome Instability in Cancer Development

Genome Instability in Cancer Development

This is thought to reflect a trait commonly referred to as ‘genome instability’, so that no two cancers are ever likely to display the exact same genetic alterations.

Author: Erich A. Nigg

Publisher: Springer Science & Business Media

ISBN: 9781402037641

Category: Medical

Page: 512

View: 140

Research over the past decades has firmly established the genetic basis of cancer. In particular, studies on animal tumour viruses and chromosome rearrangements in human tumours have concurred to identify so-called ‘proto-oncogenes’ and ‘tumour suppressor genes’, whose deregulation promotes carcinogenesis. These important findings not only explain the occurrence of certain hereditary tumours, but they also set the stage for the development of anti-cancer drugs that specifically target activated oncogenes. However, in spite of tremendous progress towards the elucidation of key signalling pathways involved in carcinogenesis, most cancers continue to elude currently available therapies. This stands as a reminder that “cancer” is an extraordinarily complex disease: although some cancers of the haematopoietic system show only a limited number of characteristic chromosomal aberrations, most solid tumours display a myriad of genetic changes and considerable genetic heterogeneity. This is thought to reflect a trait commonly referred to as ‘genome instability’, so that no two cancers are ever likely to display the exact same genetic alterations. Numerical and structural chromosome aberrations were recognised as a hallmark of human tumours for more than a century. Yet, the causes and consequences of these aberrations still remain to be fully understood. In particular, the question of how genome instability impacts on the development of human cancers continues to evoke intense debate.
Categories: Medical

Genetic Analysis of the Role of RNaseH2 in Preventing Genome Instability

Genetic Analysis of the Role of RNaseH2 in Preventing Genome Instability

One view is that defects in DNA replication are one of the main causes of genome instability. The work presented here analyzes the role of RNaseH2 in preventing genome instability.

Author: Stephanie Ruth Soltero

Publisher:

ISBN: OCLC:319538262

Category:

Page: 187

View: 101

Genome instability can arise due to the accumulation of gross chromosomal rearrangements (GCRs). Specifically, translocations, deletions, and chromosome fusions are frequent events seen in cancers with genome instability. There are multiple pathways that prevent GCRs, including S-phase cell cycle checkpoints, homologous recombination, telomere maintenance, suppression of de novo telomere addition, chromatin assembly, and mismatch repair. One view is that defects in DNA replication are one of the main causes of genome instability. The work presented here analyzes the role of RNaseH2 in preventing genome instability. RNaseH2 is involved in resolution of RNA-DNA hybrid replication intermediates that arise during Okazaki fragment processing of lagging strand DNA replication. It has been suggested that persistence of RNA-DNA hybrids can lead to genome instability because they can become mutagenic and possibly form secondary structures. It is known that there are pathways required to prevent the formation of DNA damage and there are also pathways required for dealing with the DNA damage once it becomes present, but that ultimately, both are required for prevention of genome instability. RNaseH2 is thought to be involved in preventing the formation of DNA damage. The genetic analysis presented here on rnaseh2 mutants examined what happens when there are defects in the RNaseH2 pathway thought to prevent formation of DNA damage and in addition to that when there are also defects in the pathways that are thought to prevent the accumulation of DNA damage. Additional work was done to survey a list of enriched genes that encode proteins with roles in genome instability to identify novel cellular functions important for maintenance of genome stability. The results presented in this Dissertation highlight the importance of many diverse proteins that have different cellular roles important for maintaining genome stability.
Categories:

RNA mediated Genome Instability

RNA mediated Genome Instability

This work reveals a novel mechanism by which E2 stimulation leads to genomic instability and highlights how transcriptional programs play an important role in shaping the genomic landscape of DNA damage susceptibility.

Author: Caroline Townsend Stork

Publisher:

ISBN: OCLC:951462606

Category:

Page:

View: 614

R-loops are co-transcriptional structures that form when the nascent RNA hybridizes to the complementary DNA. While R-loops serve a variety of physiological functions in regulating key cellular processes, R-loop formation has also been shown to cause DNA damage and genome instability. Specifically, loss of RNA processing and R-loop modulating factors has been shown to cause an increase in DNA damage and hyper-recombination that are R-loop dependent. The processes that contribute to R-loop formation and the mechanisms that contribute to R-loop induced DNA damage are not fully understood. In this thesis, we first examine a novel mechanism by which R-loops are processed into DNA damage. We then interrogate how changes in transcription alter R-loop levels and explore the consequences of changes in R-loop levels on DNA damage formation. In Chapter 2, we demonstrate in human cells that R-loops induced by loss of RNA processing factors, including the RNA/DNA helicases Aquarius (AQR) and Senataxin (SETX), or by the inhibition of topoisomerase I, are processed into DSBs by the nucleotide excision repair (NER) endonucleases XPF and XPG. We find that the processing of R-loops into DSBs requires the transcription-coupled NER (TC-NER) factor CSB but occurs independently of global genome repair. These findings suggest that TC-NER factors play a role in generating R-loop-induced DNA damage and genome instability. The hormone estrogen (E2) binds the estrogen receptor to promote transcription of E2-responsive genes in the breast and other tissues. E2 also has links to genomic instability and elevated E2 levels are tied to breast cancer. In Chapter 3, we show that E2 stimulation causes a rapid and global increase in the formation of R-loops. We show that E2-dependent R-loop formation is highly enriched at E2-responsive genomic loci and that E2 induces DNA replication-dependent double-strand breaks (DSBs). Strikingly, many of the DSBs that accumulate in response to E2 are R-loop dependent. Thus, R-loops resulting from the E2 transcriptional response are a significant source of DNA damage. This work reveals a novel mechanism by which E2 stimulation leads to genomic instability and highlights how transcriptional programs play an important role in shaping the genomic landscape of DNA damage susceptibility. Taken together, these findings offer insight into the role of elevated transcription and RNA processing factors in R-loop formation and demonstrate a novel mechanism by which R-loops are processed into DNA damage.
Categories:

Cancer Cell Structures Carcinogens and Genomic Instability

Cancer  Cell Structures  Carcinogens and Genomic Instability

This volume presents a collection of articles aimed at the question by what genetic or epigenetic mechanisms carcinogens can cause morphological abnormalities of tumor cells.

Author: Leon P. Bignold

Publisher: Springer Science & Business Media

ISBN: 3764371560

Category: Medical

Page: 375

View: 655

Tumors can be induced by a variety of physical and chemical carcinogens. The resulting tumor cells are usually abnormal in their morphology and behavior and transmit their abnormalities to their daughter tumor cells. Most theories of the pathogenesis of tumors suggest that carcinogens in some way cause alterations either of the genomes or of inheritable patterns of gene expression in normal cells, which then cause morphological and behavioral changes. This volume presents a collection of articles aimed at the question by what genetic or epigenetic mechanisms carcinogens can cause morphological abnormalities of tumor cells. It includes reviews of cellular targets of known carcinogens, and presents varying viewpoints of how morphological abnormalities and the actions of carcinogens might be related. The volume will be of interest to all those who are involved in cancer research or in the prevention, diagnosis or management of tumors in humans or animals.
Categories: Medical

Genome Instability and Transgenerational Effects

Genome Instability and Transgenerational Effects

In this book, we will describe various phenomena associated with the maintenance of genome stability.

Author: Igor Kovalchuk

Publisher: Nova Science Pub Incorporated

ISBN: 1608768317

Category: Medical

Page: 472

View: 909

Genome stability of every species depends on complex interaction of predefined and environmentally induced genetic and epigenetic states. Predefined states consist of chromatin structure and cell metabolic processes such as DNA repair, radical scavenging and cell signalling, whereas induced states depend on interactions with the environment. Organisms are able to respond to a changing environment by various alterations in their somatic cells as well as in their germline and progeny. In this book, we will describe various phenomena associated with the maintenance of genome stability. These include genetic and epigenetic responses to various stresses in exposed cells and organisms, bystander and, bystander-like effects, transgenerational changes in genome stability and stress tolerance in bacteria, plants and animals.
Categories: Medical

Genome Stability and Human Diseases

Genome Stability and Human Diseases

Genome instability refers to an accelerated rate of mutagenesis (Lengauer et al., 1998). There are two main types of genomic instability seen in human cancers (Cahill et al., 1999; Lengauer et al., 1998), (i) microsatellite ...

Author: Heinz-Peter Nasheuer

Publisher: Springer Science & Business Media

ISBN: 9048134714

Category: Medical

Page: 340

View: 106

Since the establishment of the DNA structure researchers have been highly interested in the molecular basis of the inheritance of genes and of genetic disorders. Scientific investigations of the last two decades have shown that, in addition to oncogenic viruses and signalling pathways alterations, genomic instability is important in the development of cancer. This view is supported by the findings that aneuploidy, which results from chromosome instability, is one of the hallmarks of cancer cells. Chromosomal instability also underpins our fundamental principles of understanding tumourigenesis: It thought that cancer arises from the sequential acquisition of genetic alterations in specific genes. In this hypothesis, these rare genetic events represent rate-limiting ‘bottlenecks’ in the clonal evolution of a cancer, and pre-cancerous cells can evolve into neoplastic cells through the acquisition of somatic mutations. This book is written by international leading scientists in the field of genome stability. Chapters are devoted to genome stability and anti-cancer drug targets, histone modifications, chromatin factors, DNA repair, apoptosis and many other key areas of research. The chapters give insights into the newest development of the genome stability and human diseases and bring the current understanding of the mechanisms leading to chromosome instability and their potential for clinical impact to the reader.
Categories: Medical

Genome Stability

Genome Stability

Restarting DNA replication by recombination -- Double-strand break repair pathways -- RecA/Rad51 and the search for homology -- Preparation of the RecA/Rad51 filament -- Single-strand annealing -- Gene conversion -- "In vivo biochemistry" : ...

Author: James Haber

Publisher: Garland Pub

ISBN: 0815344856

Category: Science

Page: 399

View: 522

"Genome Stability: DNA Repair and Recombination describes the various mechanisms of repairing DNA damage by recombination, most notably the repair of chromosomal breaks. The text presents a definitive history of the evolution of molecular models of DNA repair, emphasizing current research. The book introduces the central players in recombination. An overview of the four major pathways of homologous recombinational repair is followed by a description of the several mechanisms of nonhomologous end-joining. Designed as a textbook for advanced undergraduate and graduate students with a molecular biology and genetics background, researchers and practitioners, especially in cancer biology, will also appreciate the book as a reference"--Provided by publisher.
Categories: Science