For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
10
views
107
references
 Top references
cited by
32
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      216
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Keeping ribosomal DNA intact: a repeating challenge

      review-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          More than half of the human genome consists of repetitive sequences, with the ribosomal DNA (rDNA) representing two of the largest repeats. Repetitive rDNA sequences may form a threat to genomic integrity and cellular homeostasis due to the challenging aspects of their transcription, replication, and repair. Predisposition to cancer, premature aging, and neurological impairment in ataxia-telangiectasia and Bloom syndrome, for instance, coincide with increased cellular rDNA repeat instability. However, the mechanisms by which rDNA instability contributes to these hereditary syndromes and tumorigenesis remain unknown. Here, we review how cells govern rDNA stability and how rDNA break repair influences expansion and contraction of repeat length, a process likely associated with human disease. Recent advancements in CRISPR-based genome engineering may help to explain how cells keep their rDNA intact in the near future.

          Related collections

          Most cited references107

          • Record: found
          • Abstract: found
          • Article: not found

          Persistent DNA damage signaling triggers senescence-associated inflammatory cytokine secretion

          Francis Rodier, Jean-Philippe Coppe, Christopher K Patil … (2009)
          Cellular senescence suppresses cancer by stably arresting the proliferation of damaged cells1. Paradoxically, senescent cells also secrete factors that alter tissue microenvironments2. The pathways regulating this secretion are unknown. We show that damaged human cells develop persistent chromatin lesions bearing hallmarks of DNA double-strand breaks (DSBs), which initiate increased secretion of inflammatory cytokines such as interleukin-6 (IL-6). Cytokine secretion occurred only after establishment of persistent DNA damage signaling, usually associated with senescence, not after transient DNA damage responses (DDR). Initiation and maintenance of this cytokine response required the DDR proteins ATM, NBS1 and CHK2, but not the cell cycle arrest enforcers p53 and pRb. ATM was also essential for IL-6 secretion during oncogene-induced senescence and by damaged cells that bypass senescence. Further, DDR activity and IL-6 were elevated in human cancers, and ATM-depletion suppressed the ability of senescent cells to stimulate IL-6-dependent cancer cell invasiveness. Thus, in addition to orchestrating cell cycle checkpoints and DNA repair, a novel and important role of the DDR is to allow damaged cells to communicate their compromised state to the surrounding tissue.
          Article 0 comments Cited 766 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The multifunctional nucleolus.

            Francois-Michel Boisvert, Silvana van Koningsbruggen, Joaquín Navascués … (2007)
            The nucleolus is a distinct subnuclear compartment that was first observed more than 200 years ago. Nucleoli assemble around the tandemly repeated ribosomal DNA gene clusters and 28S, 18S and 5.8S ribosomal RNAs (rRNAs) are transcribed as a single precursor, which is processed and assembled with the 5S rRNA into ribosome subunits. Although the nucleolus is primarily associated with ribosome biogenesis, several lines of evidence now show that it has additional functions. Some of these functions, such as regulation of mitosis, cell-cycle progression and proliferation, many forms of stress response and biogenesis of multiple ribonucleoprotein particles, will be discussed, as will the relation of the nucleolus to human diseases.
            Article 0 comments Cited 516 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Regulation of DNA double-strand break repair pathway choice.

              Meena Shrivastav, Leyma P. De Haro, Jac A. Nickoloff (2008)
              DNA double-strand breaks (DSBs) are critical lesions that can result in cell death or a wide variety of genetic alterations including large- or small-scale deletions, loss of heterozygosity, translocations, and chromosome loss. DSBs are repaired by non-homologous end-joining (NHEJ) and homologous recombination (HR), and defects in these pathways cause genome instability and promote tumorigenesis. DSBs arise from endogenous sources including reactive oxygen species generated during cellular metabolism, collapsed replication forks, and nucleases, and from exogenous sources including ionizing radiation and chemicals that directly or indirectly damage DNA and are commonly used in cancer therapy. The DSB repair pathways appear to compete for DSBs, but the balance between them differs widely among species, between different cell types of a single species, and during different cell cycle phases of a single cell type. Here we review the regulatory factors that regulate DSB repair by NHEJ and HR in yeast and higher eukaryotes. These factors include regulated expression and phosphorylation of repair proteins, chromatin modulation of repair factor accessibility, and the availability of homologous repair templates. While most DSB repair proteins appear to function exclusively in NHEJ or HR, a number of proteins influence both pathways, including the MRE11/RAD50/NBS1(XRS2) complex, BRCA1, histone H2AX, PARP-1, RAD18, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and ATM. DNA-PKcs plays a role in mammalian NHEJ, but it also influences HR through a complex regulatory network that may involve crosstalk with ATM, and the regulation of at least 12 proteins involved in HR that are phosphorylated by DNA-PKcs and/or ATM.
              Article 0 comments Cited 405 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Daniël O. Warmerdam:
                ORCID: http://orcid.org/0000-0003-1606-7448
                +31 205664671 , d.o.warmerdam@amc.uva.nl
                Journal
                Journal ID (nlm-ta): Chromosome Res
                Journal ID (iso-abbrev): Chromosome Res
                Title: Chromosome Research
                Publisher: Springer Netherlands (Dordrecht )
                ISSN (Print): 0967-3849
                ISSN (Electronic): 1573-6849
                Publication date (Electronic): 17 December 2018
                Publication date PMC-release: 17 December 2018
                Publication date (Print): 2019
                Volume: 27
                Issue: 1
                Pages: 57-72
                Affiliations
                [1 ]CRISPR Platform, University of Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
                [2 ]Section of Oncogenetics, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, de Boelelaan 1117, 1081 HV Amsterdam, the Netherlands
                Author notes

                Responsible Editors: Jennifer Gerton and Lev Porokhovnik

                Author information
                http://orcid.org/0000-0003-1606-7448
                Article
                Publisher ID: 9594
                DOI: 10.1007/s10577-018-9594-z
                PMC ID: 6394564
                PubMed ID: 30556094
                SO-VID: 5fc0fa17-4dda-4055-9ae8-7b131e6f56b7
                Copyright © © The Author(s) 2018
                License:

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Date received : 3 September 2018
                Date revision received : 20 November 2018
                Date accepted : 29 November 2018
                Funding
                Funded by: Academic Medical Center (AMC)
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © Springer Nature B.V. 2019

                ScienceOpen disciplines: Genetics
                Keywords: repetitive dna,ribosomal dna,dna repair,dna repeat integrity,bloom syndrome,ataxia-telangiectasia,genomic instability,crispr
                Data availability:
                ScienceOpen disciplines: Genetics
                Keywords: repetitive dna, ribosomal dna, dna repair, dna repeat integrity, bloom syndrome, ataxia-telangiectasia, genomic instability, crispr

                Comments

                Comment on this article

                scite_

                Similar content216

                See all similar

                Cited by31

                See all cited by

                Most referenced authors2,243

                See all reference authors