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Nucleolar organizer regions: genomic 'dark matter' requiring illumination

Genes & development, 2016-07, Vol.30 (14), p.1598-1610 [Peer Reviewed Journal]

2016 McStay; Published by Cold Spring Harbor Laboratory Press. ;2016 ;ISSN: 0890-9369 ;EISSN: 1549-5477 ;DOI: 10.1101/gad.283838.116 ;PMID: 27474438

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  • Title:
    Nucleolar organizer regions: genomic 'dark matter' requiring illumination
  • Author: McStay, Brian
  • Subjects: Aging ; Animals ; Arabidopsis ; Chromosomes - metabolism ; DNA Breaks, Double-Stranded ; DNA, Ribosomal - metabolism ; Drosophila ; Genome, Human - genetics ; Genomic Instability ; Humans ; Metazoa ; Nucleolus Organizer Region - genetics ; Nucleolus Organizer Region - physiology ; Review ; Saccharomyces cerevisiae
  • Is Part Of: Genes & development, 2016-07, Vol.30 (14), p.1598-1610
  • Description: Nucleoli form around tandem arrays of a ribosomal gene repeat, termed nucleolar organizer regions (NORs). During metaphase, active NORs adopt a characteristic undercondensed morphology. Recent evidence indicates that the HMG-box-containing DNA-binding protein UBF (upstream binding factor) is directly responsible for this morphology and provides a mitotic bookmark to ensure rapid nucleolar formation beginning in telophase in human cells. This is likely to be a widely employed strategy, as UBF is present throughout metazoans. In higher eukaryotes, NORs are typically located within regions of chromosomes that form perinucleolar heterochromatin during interphase. Typically, the genomic architecture of NORs and the chromosomal regions within which they lie is very poorly described, yet recent evidence points to a role for context in their function. In Arabidopsis, NOR silencing appears to be controlled by sequences outside the rDNA (ribosomal DNA) array. Translocations reveal a role for context in the expression of the NOR on the X chromosome in Drosophila Recent work has begun on characterizing the genomic architecture of human NORs. A role for distal sequences located in perinucleolar heterochromatin has been inferred, as they exhibit a complex transcriptionally active chromatin structure. Links between rDNA genomic stability and aging in Saccharomyces cerevisiae are now well established, and indications are emerging that this is important in aging and replicative senescence in higher eukaryotes. This, combined with the fact that rDNA arrays are recombinational hot spots in cancer cells, has focused attention on DNA damage responses in NORs. The introduction of DNA double-strand breaks into rDNA arrays leads to a dramatic reorganization of nucleolar structure. Damaged rDNA repeats move from the nucleolar interior to form caps at the nucleolar periphery, presumably to facilitate repair, suggesting that the chromosomal context of human NORs contributes to their genomic stability. The inclusion of NORs and their surrounding chromosomal environments in future genome drafts now becomes a priority.
  • Publisher: United States: Cold Spring Harbor Laboratory Press
  • Language: English
  • Identifier: ISSN: 0890-9369
    EISSN: 1549-5477
    DOI: 10.1101/gad.283838.116
    PMID: 27474438
  • Source: GFMER Free Medical Journals
    MEDLINE
    PubMed Central
    Alma/SFX Local Collection
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