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      Chromatin and nucleosome dynamics in DNA damage and repair

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          Abstract

          This review by Hauer and Gasser presents an overview of the function of chromatin structure and its dynamic changes in response to genotoxic stress, focusing on both subnuclear organization and the physical mobility of DNA, and discusses the link between enhanced chromatin dynamics and histone loss.

          Abstract

          Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin structure and its dynamic changes in response to genotoxic stress, focusing on both subnuclear organization and the physical mobility of DNA. We review the requirements and mechanisms that cause chromatin relocation, enhanced mobility, and chromatin unfolding as a consequence of genotoxic lesions. An intriguing link has been established recently between enhanced chromatin dynamics and histone loss.

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          The DNA-damage response in human biology and disease.

          Stephen P. Jackson, Jiri Bartek (2009)
          The prime objective for every life form is to deliver its genetic material, intact and unchanged, to the next generation. This must be achieved despite constant assaults by endogenous and environmental agents on the DNA. To counter this threat, life has evolved several systems to detect DNA damage, signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management.
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            The biology of chromatin remodeling complexes.

            Cedric R Clapier, Bradley Cairns (2009)
            The packaging of chromosomal DNA by nucleosomes condenses and organizes the genome, but occludes many regulatory DNA elements. However, this constraint also allows nucleosomes and other chromatin components to actively participate in the regulation of transcription, chromosome segregation, DNA replication, and DNA repair. To enable dynamic access to packaged DNA and to tailor nucleosome composition in chromosomal regions, cells have evolved a set of specialized chromatin remodeling complexes (remodelers). Remodelers use the energy of ATP hydrolysis to move, destabilize, eject, or restructure nucleosomes. Here, we address many aspects of remodeler biology: their targeting, mechanism, regulation, shared and unique properties, and specialization for particular biological processes. We also address roles for remodelers in development, cancer, and human syndromes.
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              The DNA damage response: making it safe to play with knives.

              Alberto Ciccia, Stephen J. Elledge (2010)
              Damage to our genetic material is an ongoing threat to both our ability to faithfully transmit genetic information to our offspring as well as our own survival. To respond to these threats, eukaryotes have evolved the DNA damage response (DDR). The DDR is a complex signal transduction pathway that has the ability to sense DNA damage and transduce this information to the cell to influence cellular responses to DNA damage. Cells possess an arsenal of enzymatic tools capable of remodeling and repairing DNA; however, their activities must be tightly regulated in a temporal, spatial, and DNA lesion-appropriate fashion to optimize repair and prevent unnecessary and potentially deleterious alterations in the structure of DNA during normal cellular processes. This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals. Copyright © 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Genes Dev
                Journal ID (iso-abbrev): Genes Dev
                Journal ID (hwp): genesdev
                Journal ID (pmc): genesdev
                Journal ID (publisher-id): GAD
                Title: Genes & Development
                Publisher: Cold Spring Harbor Laboratory Press
                ISSN (Print): 0890-9369
                ISSN (Electronic): 1549-5477
                Publication date (Print): 15 November 2017
                Volume: 31
                Issue: 22
                Pages: 2204-2221
                Affiliations
                [1 ]Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland;
                [2 ]Faculty of Natural Sciences, University of Basel, CH-4056 Basel, Switzerland
                Author notes
                [3]

                Present address: Department of Molecular Mechanisms of Disease, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, CH-8057 Zurich, Switzerland.

                Corresponding author: susan.gasser@ 123456fmi.ch
                Article
                Medline ID: 8711660
                DOI: 10.1101/gad.307702.117
                PMC ID: 5769766
                PubMed ID: 29284710
                SO-VID: 6be84b06-dea2-4a20-ae08-0dc21140991b
                Copyright © © 2017 Hauer and Gasser; Published by Cold Spring Harbor Laboratory Press
                License:

                This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Page count
                Pages: 18
                Funding
                Funded by: Boehringer Ingelheim Fonds , open-funder-registry 10.13039/501100001645;
                Funded by: Human Frontiers Science Program
                Funded by: Swiss National Science Foundation , open-funder-registry 10.13039/100000001;
                Funded by: Swiss Cancer League
                Funded by: Novartis Research Foundation
                Categories
                Subject: 2
                Subject: Review

                Keywords: chromatin structure,histones,nuclear organization,dna damage,nucleosome remodelers
                Data availability:
                Keywords: chromatin structure, histones, nuclear organization, dna damage, nucleosome remodelers

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