Opposing role of condensin and radiation-sensitive gene RAD52 in ribosomal DNA stability regulation.
Blocking target of rapamycin signaling by starvation or rapamycin inhibits ribosomal DNA (rDNA) transcription and causes condensin-mediated rDNA condensation and nucleolar contraction. In the absence of condensin, however, repression of rDNA transcription leads to rDNA instability and elevated level of extrachromosomal rDNA circles and nucleolar fragmentation. Here, we show that mutations in the Rad52 homologous recombination machinery block rDNA instability. Rad52 is normally excluded from the nucleolus. In the absence of condensin, however, repression of rDNA transcription results in Rad52 localization to the nucleolus, association with rDNA and subsequent formation of extrachromosomal rDNA circles, and reduced cell survival. In contrast, deletion of RAD52 restores cell viability under the same conditions. These results reveal an opposing role of condensin and Rad52 in the control of rDNA stability under nutrient starvation conditions.
Tsang
Chi Kwan
CK
Department of Pharmacology and Cancer Institute of New Jersey, the University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
Zheng
X F Steven
XFS
Department of Pharmacology and Cancer Institute of New Jersey, the University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects; D004256:DNA Polymerase I / Q000378:metabolism; D004275:DNA, Ribosomal / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004843:Epistasis, Genetic; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D051721:Rad52 DNA Repair and Recombination Protein / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; C108312:condensin complexes; D004247:DNA; D004256:DNA Polymerase I; D000251:Adenosine Triphosphatases; D020123:Sirolimus