scholarly journals Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matías Capella ◽  
Imke K. Mandemaker ◽  
Lucía Martín Caballero ◽  
Fabian den Brave ◽  
Boris Pfander ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Homologous Recombination ◽  
Ribosomal Rna ◽  
Molecular Mechanisms ◽  
Human Cells ◽  
Ribosomal Rna Genes ◽  
Genome Integrity ◽  
Repetitive Nature ◽  
Rna Genes

AbstractRibosomal RNA genes (rDNA) are highly unstable and susceptible to rearrangement due to their repetitive nature and active transcriptional status. Sequestration of rDNA in the nucleolus suppresses uncontrolled recombination. However, broken repeats must be first released to the nucleoplasm to allow repair by homologous recombination. Nucleolar release of broken rDNA repeats is conserved from yeast to humans, but the underlying molecular mechanisms are currently unknown. Here we show that DNA damage induces phosphorylation of the CLIP-cohibin complex, releasing membrane-tethered rDNA from the nucleolus in Saccharomyces cerevisiae. Downstream of phosphorylation, SUMOylation of CLIP-cohibin is recognized by Ufd1 via its SUMO-interacting motif, which targets the complex for disassembly through the Cdc48/p97 chaperone. Consistent with a conserved mechanism, UFD1L depletion in human cells impairs rDNA release. The dynamic and regulated assembly and disassembly of the rDNA-tethering complex is therefore a key determinant of nucleolar rDNA release and genome integrity.

scholarly journals Relocation of rDNA repeats for repair is dependent on SUMO-mediated nucleolar release by the Cdc48/p97 segregase

2021 ◽  
Author(s):  
Matías Capella ◽  
Imke K. Mandemaker ◽  
Lucía Martín Caballero ◽  
Boris Pfander ◽  
Andreas G. Ladurner ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Homologous Recombination ◽  
Ribosomal Rna ◽  
Nuclear Membrane ◽  
Molecular Mechanisms ◽  
Genome Integrity ◽  
Repetitive Nature ◽  
Active Transcription ◽  
Rna Genes

AbstractRibosomal RNA genes (rDNA) are highly unstable and susceptible to rearrangement due to active transcription and their repetitive nature. Compartmentalization of rDNA in the nucleolus suppresses uncontrolled recombination. However, broken repeats must be released to the nucleoplasm to allow repair by homologous recombination. The process of rDNA relocation is conserved from yeast to humans, but the underlying molecular mechanisms are currently unknown. Here we show that DNA damage induces phosphorylation of the CLIP component Nur1, releasing nuclear membrane-tethered rDNA repeats from the nucleolus in Saccharomyces cerevisiae. Cooperating with Nur1 phosphorylation, SUMOylation targets the rDNA tethering complex for disassembly mediated by the segregase Cdc48/p97, which recognizes SUMOylated CLIP-cohibin through its cofactor, Ufd1. Consistent with the conservation of this mechanism, UFD1L depletion impairs rDNA release in human cells. The dynamic and regulated assembly and disassembly of the CLIP-cohibin complex is therefore a key, conserved determinant of nucleolar rDNA release and genome integrity.

scholarly journals DNA methylation in the promoter of ribosomal RNA genes in human cells as determined by genomic sequencing

FEBS Letters ◽  
1996 ◽  
Vol 388 (2-3) ◽  
pp. 192-194 ◽  
Author(s):  
Stefan Kochanek ◽  
Keiichi Hosokawa ◽  
Gudrun Schiedner ◽  
Doris Renz ◽  
Walter Doerfler
Keyword(s):  
Dna Methylation ◽  
Ribosomal Rna ◽  
Human Cells ◽  
Ribosomal Rna Genes ◽  
Genomic Sequencing ◽  
Rna Genes

THE STRUCTURE OF THE RIBOSOMAL RNA GENES OF THE YEAST SACCHAROMYCES CEREVISIAE

1978 ◽  
pp. 445-461 ◽  
Author(s):  
Graeme I. Bell ◽  
Alejandro Venegas ◽  
Pablo Valenzuela ◽  
Frank R. Masiarz ◽  
Louis J. De Gennaro ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ribosomal Rna ◽  
Ribosomal Rna Genes ◽  
Yeast Saccharomyces Cerevisiae ◽  
Rna Genes
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