Dna Damage Responses
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Dna Damage Responses
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Author : Nima Mosammaparast
language : en
Publisher:
Release Date : 2022
Dna Damage Responses written by Nima Mosammaparast and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022 with DNA damage categories.
This volume provides detailed methods and key approaches used to mechanistically study DNA damage, as well as the factors involved in the damage response. Chapters guide readers through proteomics and biophysical approaches, analyzing protein function, quantifying DNA replication dynamics and nucleic acid base damage, as well as biochemical reconstitution of key pathways involved in DNA repair. 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, DNA Damage Responses: Methods and Protocols aims to be a useful practical guide to researches to help further their study in this field.
The Dna Damage Response Implications On Cancer Formation And Treatment
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Author : Kum Kum Khanna
language : en
Publisher: Springer Science & Business Media
Release Date : 2009-09-18
The Dna Damage Response Implications On Cancer Formation And Treatment written by Kum Kum Khanna and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-09-18 with Medical categories.
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.
Exploiting Dna Damage Response In The Era Of Precision Oncology
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Author : Yitzhak Zimmer
language : en
Publisher: Frontiers Media SA
Release Date : 2020-12-11
Exploiting Dna Damage Response In The Era Of Precision Oncology written by Yitzhak Zimmer and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-12-11 with Medical categories.
Topic Editor Christian Reinhardt has received funding from companies Gilead, and lecture fees from Abbvie, Merck, and AstraZeneca. All other topic editors declare no competing interests with regards to the Research Topic subject.
The Role Of Different Subcellular Organelles In Dna Damage Response
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Author : Guoping Zhao
language : en
Publisher: Frontiers Media SA
Release Date : 2021-12-30
The Role Of Different Subcellular Organelles In Dna Damage Response written by Guoping Zhao and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-12-30 with Science categories.
Targeting The Dna Damage Response For Anti Cancer Therapy
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Author : John Pollard
language : en
Publisher: Springer
Release Date : 2018-05-26
Targeting The Dna Damage Response For Anti Cancer Therapy written by John Pollard and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-05-26 with Medical categories.
Over the past decade a complex role for DNA damage response (DDR) in tumorigenesis has emerged. A proficient DDR has been shown to be a primary cause for cellular resistance to the very many DNA damaging drugs, and IR, that are widely used as standard-of-care across multiple cancer types. It has also been shown that defects in this network, predominantly within the ATM mediated signaling pathway, are commonly observed in cancers and may be a primary event during tumorigenesis. Such defects may promote a genomically unstable environment, facilitating the persistence of mutations, any of which may provide a growth or survival advantage to the developing tumor. In addition, these somatic defects provide opportunities to exploit a reliance on remaining repair pathways for survival, a process which has been termed synthetic lethality. As a result of all these observations there has been a great interest in targeting the DDR to provide anti-cancer agents that may have benefit as monotherapy in cancers with high background DNA damage levels or as a means to increase the efficacy of DNA damaging drugs and IR. In this book we will review a series of important topics that are of great interest to a broad range of academic, industrial and clinical researchers, including the basic science of the DDR, its role in tumorigenesis and in dictating response to DNA damaging drugs and IR. Additionally, we will focus on the several proteins that have been targeted in attempts to provide drug candidates, each of which appear to have quite distinct profiles and could represent very different opportunities to provide patient benefit.
Biological Responses To Dna Damage
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Author :
language : en
Publisher: CSHL Press
Release Date : 2000
Biological Responses To Dna Damage written by and has been published by CSHL Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000 with DNA damage categories.
Living cells have evolved many ways of coping with metabolic events and environmental influences that damage DNA. These mechanisms, and the frequent progression to cancer that results when they go awry, are rev iewed in this volume by authors from over sixty of the world's leading laboratories. The topics discussed include DNA repair, mutagenesis and other damage-tolerance functions, checkpoint control, apoptosis, and adaptation. They draw from studies on human and yeast cells. Current, but with a valuable historical perspective, this volume has the depth and lasting value typical of this most prestigious series and is esse ntial reading for investigators of DNA replication, cell cycle control, and tumorigenesis.
Grappling With The Multifaceted World Of The Dna Damage Response
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Author : Antonio Porro
language : en
Publisher: Frontiers Media SA
Release Date : 2017-01-10
Grappling With The Multifaceted World Of The Dna Damage Response written by Antonio Porro and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-01-10 with Electronic book categories.
DNA damage is a major threat to genomic integrity and cell survival. It can arise both spontaneously and in response to exogenous agents. DNA damage can attack most parts of the DNA structure, ranging from minor and major chemical modifications, to single-strand breaks (SSBs) and gaps, to full double-strand breaks (DSBs). If DNA injuries are mis-repaired or unrepaired, they may ultimately result in mutations or wider-scale genome aberrations that threaten cell homeostasis. Consequently, the cells elicit an elaborate signalling network, known as DNA damage response (DDR), to detect and repair these cytotoxic lesions. This Research Topic was aimed at comprehensive investigations of basic and novel mechanisms that underlie the DNA damage response in eukaryotes.
Ubiquitin And Ubiquitin Relative Sumo In Dna Damage Response
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Author : Kristijan Ramadan
language : en
Publisher: Frontiers Media SA
Release Date : 2018-02-09
Ubiquitin And Ubiquitin Relative Sumo In Dna Damage Response written by Kristijan Ramadan and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-02-09 with categories.
DNA damage response (DDR) is a term that includes a variety of highly sophisticated mechanisms that cells have evolved in safeguarding the genome from the deleterious consequences of DNA damage. It is estimated that every single cell receives tens of thousands of DNA lesions per day. Failure of DDR to properly respond to DNA damage leads to stem cell dysfunction, accelerated ageing, various degenerative diseases or cancer. The sole function of DDR is to recognize diverse DNA lesions, signal their presence, activate cell cycle arrest and finally recruit specific DNA repair proteins to fix the DNA damage and thus prevent genomic instability. DDR is composed of hundreds of spatiotemporally regulated and interconnected proteins, which are able to promptly respond to various DNA lesions. So it is not surprising that mutations in genes encoding various DDR proteins cause embryonic lethality, malignancies, neurodegenerative diseases and premature ageing. The importance of DDR for cell survival and genome stability is unquestionable, but how the sophisticated network of hundreds of different DDR proteins is spatiotemporally coordinated is far from being understood. In the last ten years ubiquitin (ubiquitination) and the ubiquitin-relative SUMO (sumoylation) have emerged as essential posttranslational modifications that regulate DDR. Beside a plethora of ubiqutin and sumo E1-activating enzymes, E2-conjugating enzymes, E3-ligases and ubiquitin/sumo proteases involved in ubiquitination and sumoylation, the complexity of ubiqutin and sumo systems is additionally increased by the fact that both ubiquitin and sumo can form a variety of different chains on substrates which govern the substrate fate, such as its interaction with other proteins, changing its enzymatic activity or promoting substrate degradation. The importance of ubiquitin/SUMO systems in the orchestration of DDR is best illustrated in patients with mutations in E3-ubiquitin ligases BRCA1 or RNF168. BRCA1 is essential for proper function of DDR and its mutations lead to triple-negative breast and ovarian cancers. RNF168 is an E3 ubiquitin ligase, which creates the ubiquitin docking platform for recruitment of different DNA damage signalling and repair proteins at sites of DNA lesion, and its mutations cause RIDDLE syndrome characterized by radiosensitivity, immunodeficiency and learning disability. In addition, recently discovered the ubiquitin receptor protein SPRTN is part of the DNA replication machinery and its mutations cause early-onset hepatocellular carcinoma and premature ageing in humans. Despite more than 700 different enzymes directly involved in ubiquitination and sumoylation processes only few of them are known to play a role in DDR. Therefore, we feel that the role of ubiquitin and the ubiquitin-related SUMO in DDR is far from being understood, and that this is the emerging field that will hugely expand in the next decade due to the rapid development of a new generation of technologies, which will allow us a more robust and precise analyses of human genome, transcriptome and proteome. In this Research Topic we provide a comprehensive overview of our current understanding of ubiquitin and SUMO pathways in all aspects of DDR, from DNA replication to different DNA repair pathways, and demonstrate how alterations in these pathways cause genomic instability that is linked to degenerative diseases, cancer and pathological ageing.
Cancer Associated Defects In The Dna Damage Response Drivers For Malignant Transformation And Potential Therapeutic Targets
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Author : Marcel van Vugt
language : en
Publisher: Frontiers Media SA
Release Date : 2016-10-17
Cancer Associated Defects In The Dna Damage Response Drivers For Malignant Transformation And Potential Therapeutic Targets written by Marcel van Vugt and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-10-17 with Genetics categories.
For this eBook, and the associated Research Topic in Frontiers in Genetics, entitled: ‘Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets’ we have selected 10 papers that each discusses important, yet distinct aspects of the response to DNA damage in normal cells and cancer cells. Using an evolutionary conserved signaling network called the ‘DNA damage response (DDR)’ cells maintain the integrity of their genome, and thus safeguard cellular functioning and the ability to create viably progeny. Initially, the DDR appeared to consist of few linear kinase-driven pathways. However, research over the past decades in model organisms, as well as in the human system has revealed that the DDR is a complex signaling network, wired by multiple parallel pathways and displaying extensive crosstalk. Besides phosphorylation, multiple other post-translational modifications, including ubiquitination and sumoylation, are involved to achieve chromatin remodeling and initiation of DNA repair. Also, rather than being a cell-intrinsic phenomenon, we increasingly appreciate that cell-cell communication is involved. The recognition and repair of DNA damage is essential to maintain normal physiology. Multiple pathological conditions have been attributed to defective DNA repair, most notably accelerated aging, neurodegeneration and cancer. In the context of cancer, through repair of DNA damage or elimination of irreparably damaged cells, the DDR clearly has a tumor-suppressive role. Indeed, many tumor cells show partially inactivated DDR signaling, which allows proliferation in the context of DNA damage-inducing oncogenes. Simultaneously, loss of specific DDR signaling nodes creates a specific dependence of tumor cells on their remaining DDR components, and thus creates therapeutic opportunities. Especially in the context of cancer treatment, numerous targeted agents are under investigation, either to potentiate the cytotoxic effects of chemo-radiotherapy, or to induce synthetic lethality with cancer-specific alterations, with the treatment of BRCA1/2 mutant cancers with PARP1 inhibitors as a prototype example. We have selected four review articles that provide insight into the key components and the wiring of the DDR and DNA repair. Torgovnick and Schumacher review the involvement of DNA repair in the initiation and treatment of cancer, Brinkmann et al., describe the involvement of ubiquitination in DNA damage signaling and Jaiswal and Lindqvist discuss how cell-extrinsic signaling participates in communication of DNA damage to neighboring cells. In addition, Shatneyeva and colleagues review the connection between the cellular response to DNA damage and escape from immune surveillance. Concerning the therapeutic application of targeting the DDR and DNA repair, three articles were included. Krajewska and van Vugt review the wiring of homologous recombination and how this offers therapeutic opportunities. Additionally, Knittel and colleagues describe how genetic loss of the central DDR component ATM in chronic lymphocytic leukemia can be exploited therapeutically by targeting certain parallel DNA repair pathways. Syljuasen and colleagues report on how targeting of the DDR can be used as a therapeutic strategy in lung cancer. Finally, three chapters describe newly identified regulators of the cellular response to DNA damage. Von Morgen et al. describe the R2TP complex, Lezzi and Fanciluuli review the involvement of Che-1/AATF in the DDR, and Ohms and co-authors describe how retrotransposons are at the basis of increased genomic instability. Altogether, these articles describe how defective responses to DNA damage underlie disease - and especially in the context of cancer -can be exploited to better treat disease.
Proceedings From Accm19 Cell Cycle Dna Damage Response And Telomeres
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Author : Andrew Burgess
language : en
Publisher: Frontiers Media SA
Release Date : 2020-11-18
Proceedings From Accm19 Cell Cycle Dna Damage Response And Telomeres written by Andrew Burgess and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-11-18 with Science categories.
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.