This volume describes the elaborate surveillance systems and various DNA repair mechanisms that ensure accurate passage of genetic information onto daughter cells. In particular, it narrates how the cell cycle checkpoint and DNA repair machineries detect and restore DNA damages that are embedded in millions to billions of normal base pairs. The scope of the book ranges from biochemical analyses and structural details of DNA repair proteins, to integrative genomics and population-based studies. It provides a snapshot of current understanding about some of the major DNA repair pathways, including base-excision repair, nucleotide excision repair, mismatch repair, homologous recombination, and non-homologous end-joining as well as cell cycle checkpoints and translesion DNA synthesis. One of the particular emphases of the book is the link between inherited DNA repair deficiencies and susceptibility to cancer in the general population. For the first time, the book brings together a collection of review articles written by a group of active and laboratory-based investigators who have a clear understanding of the recent advances in the fields of DNA damage repair and genomic stability and their implications in carcinogenesis, new approaches in cancer therapy, and cancer prevention.

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.

The ?eld of cellular responses to DNA damage has attained widespread recognition and interest in recent years commensurate with its fundamental role in the ma- tenance of genomic stability. These responses, which are essential to preventing cellular death or malignant transformation, are organized into a sophisticated s- tem designated the “DNA damage response”. This system operates in all living organisms to maintain genomic stability in the face of constant attacks on the DNA from a variety of endogenous by-products of normal metabolism, as well as exogenous agents such as radiation and toxic chemicals in the environment. The response repairs DNA damage via an intricate cellular signal transduction network that coordinates with various processes such as regulation of DNA replication, tr- scriptional responses, and temporary cell cycle arrest to allow the repair to take place. Defects in this system result in severe genetic disorders involving tissue degeneration, sensitivity to speci?c damaging agents, immunode?ciency, genomic instability, cancer predisposition and premature aging. The ?nding that many of the crucial players involved in DNA damage response are structurally and functionally conserved in different species spurred discoveries of new players through similar analyses in yeast and mammals. We now understand the chain of events that leads to instantaneous activation of the massive cellular responses to DNA lesions. This book summarizes several new concepts in this rapidly evolving ?eld, and the advances in our understanding of the complex network of processes that respond to DNA damage.

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

As a major defence against environmental damage to cells DNA repair is present in all organisms including bacteria, yeast, drosophila, fish, amphibians, rodents and humans. DNA repair is involved in processes that minimise cell killing, mutations, replication errors, persistence of DNA damage and genomic instability. Abnormalities in these processes have been implicated in cancer and ageing. This book presents leading-edge research from around the world in this frontal field.

This textbook takes you on a journey to the basic concepts of cancer biology. It combines developmental, evolutionary and cell biology perspectives, to then wrap-up with an integrated clinical approach. The book starts with an introductory chapter, looking at cancer in a nut shell. The subsequent chapters are detailed and the idea of cancer as a mass of somatic cells undergoing a micro-evolutionary Darwinian process is explored. Further, the main Hanahan and Weinberg “Hallmarks of Cancer” are revisited. In most chapters, the fundamental experiments that led to key concepts, connecting basic biology and biomedicine are highlighted. In the book’s closing section all of these concepts are integrated in clinical studies, where molecular diagnosis as well as the various classical and modern therapeutic strategies are addressed. The book is written in an easy-to-read language, like a one-on-one conversation between the writer and the reader, without compromising the scientific accuracy. Therefore, this book is suited not only for advanced undergraduates and master students but also for patients or curious lay people looking for a further understanding of this shattering disease

This book edition is intended to provide a concise summary for select topics in DNA repair, a field that is ever-expanding in complexity and biologic significance. The topics reviewed ranged from fundamental mechanisms of DNA repair to the interface between DNA repair and a spectrum on cellular process to the clinical relevance of DNA repair in oncologic paradigms. The information in this text should provide a foundation from which one can explore the various topics in depth. The book serve as a supplementary text in seminar courses with focus on DNA repair as well as a general reference for scholars with an interest in DNA repair.