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Maintenance of Genome Integrity: DNA Damage Sensing, Signaling, Repair and Replication in Plants

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198207 Year: Pages: 129 DOI: 10.3389/978-2-88919-820-7 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Abstract

Environmental stresses and metabolic by-products can severely affect the integrity of genetic information by inducing DNA damage and impairing genome stability. As a consequence, plant growth and productivity are irreversibly compromised. To overcome genotoxic injury, plants have evolved complex strategies relying on a highly efficient repair machinery that responds to sophisticated damage perception/signaling networks. The DNA damage signaling network contains several key components: DNA damage sensors, signal transducers, mediators, and effectors. Most of these components are common to other eukaryotes but some features are unique to the plant kingdom. ATM and ATR are well-conserved members of PIKK family, which amplify and transduce signals to downstream effectors. ATM primarily responds to DNA double strand breaks while ATR responds to various forms of DNA damage. The signals from the activated transducer kinases are transmitted to the downstream cell-cycle regulators, such as CHK1, CHK2, and p53 in many eukaryotes. However, plants have no homologue of CHK1, CHK2 nor p53. The finding of Arabidopsis transcription factor SOG1 that seems functionally but not structurally similar to p53 suggests that plants have developed unique cell cycle regulation mechanism. The double strand break repair, recombination repair, postreplication repair, and lesion bypass, have been investigated in several plants. The DNA double strand break, a most critical damage for organisms are repaired non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Damage on template DNA makes replication stall, which is processed by translesion synthesis (TLS) or error-free postreplication repair (PPR) pathway. Deletion of the error-prone TLS polymerase reduces mutation frequencies, suggesting PPR maintains the stalled replication fork when TLS is not available. Unveiling the regulation networks among these multiple pathways would be the next challenge to be completed. Some intriguing issues have been disclosed such as the cross-talk between DNA repair, senescence and pathogen response and the involvement of non-coding RNAs in global genome stability. Several studies have highlighted the essential contribution of chromatin remodeling in DNA repair. DNA damage sensing, signaling and repair have been investigated in relation to environmental stresses, seed quality issues, mutation breeding in both model and crop plants and all these studies strengthen the idea that components of the plant response to genotoxic stress might represent tools to improve stress tolerance and field performance. This focus issue gives researchers the opportunity to gather and interact by providing Mini-Reviews, Commentaries, Opinions, Original Research and Method articles which describe the most recent advances and future perspectives in the field of DNA damage sensing, signaling and repair in plants. A comprehensive overview of the current progresses dealing with the genotoxic stress response in plants will be provided looking at cellular and molecular level with multidisciplinary approaches. This will hopefully bring together valuable information for both plant biotechnologists and breeders.

Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199495 Year: Pages: 107 DOI: 10.3389/978-2-88919-949-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2016-01-19 14:05:46
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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.

Die Welt reparieren

Authors: --- --- ---
Book Series: Urban Studies ISBN: 9783839433775 9783837633771 Year: Pages: 352 DOI: 10.14361/9783839433775 Language: German
Publisher: transcript Verlag Grant: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Subject: Sociology
Added to DOAB on : 2017-03-03 11:01:40
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Across the world, more and more DIY initiatives are cropping up, in which a diversity of matters and problems are being collectively dealt with. In these collaborative contexts – located away from the market and the state - an understanding of living together and urbanity based around democracy is tested out, and at the same time, ecologically and socially responsible solutions are being sought for fundamental forms of provision of food, of energy, and for making all manner of technology accessible. In the process, fascinating new forms of collective production, repairing and swapping arise which challenge the industrial logic of the 20th century, even turn them on their head. This book is dedicated to the visionary power of these promising innovative practices, and at the same time, provides a societal categorisation of the new `laboratories' of societal transformation. With photographs by Falk Messerschmidt.

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