Peer-Reviewed Journal Details
Mandatory Fields
Grob, A,Colleran, C,McStay, B
2014
February
Genes & Development
Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division
Published
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Optional Fields
nucleolus nucleolar organizer region (NOR) UBF mitotic bookmarking pseudo-NOR neo-NOR RIBOSOMAL-RNA GENE ORGANIZER REGIONS POLYMERASE-I GENOMIC ARCHITECTURE TRANSCRIPTION UBF DNA MAINTENANCE NORS CHROMOSOMES
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Human cell nuclei are functionally organized into structurally stable yet dynamic bodies whose cell cycle inheritance is poorly understood. Here, we investigate the biogenesis and propagation of nucleoli, sites of ribosome biogenesis and key regulators of cellular growth. Nucleolar and cell cycles are intimately connected. Nucleoli disappear during mitosis, reforming around prominent uncharacterized chromosomal features, nucleolar organizer regions (NORs). By examining the effects of UBF depletion on both endogenous NORs and synthetic pseudo-NORs, we reveal its essential role in maintaining competency and establishing a bookmark on mitotic NORs. Furthermore, we demonstrate that neo-NORs, UBF-binding site arrays coupled with rDNA transcription units, direct the de novo biogenesis of functional compartmentalized neonucleoli irrespective of their site of chromosomal integration. For the first time, we establish the sequence requirements for nucleolar biogenesis and provide proof that this is a staged process where UBF-dependent mitotic bookmarking precedes functiondependent nucleolar assembly.
DOI 10.1101/gad.234591.113
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