Opposing Role of Condensin and Radiation-sensitive Gene RAD52 in Ribosomal DNA Stability Regulation

Chi Kwan Tsang,X F Steven Zheng

doi:10.1074/jbc.m109.031302

Chi Kwan Tsang, X F Steven Zheng

Open Access

https://doi.org/10.1074/jbc.m109.031302

Copy DOI

Abstract

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.

Highlights

In Saccharomyces cerevisiae, there are ϳ150 copies of rDNA tandem repeats on chromosome XII
Brewer and colleagues [6] showed that Ͼ80% of the chromosomal copies of the rDNA repeats are deleted in a rpa135 mutant. (RPA135 encodes the second largest polymerases I (Pol I) subunit.) Another study showed that in an rpa135 mutant, in which 35 S rRNA is synthesized by Pol II from a multicopy plasmid, more than one-half of the chromosomal rDNA repeats were reduced under the condition that represses Pol I transcription [4]
We show that when rDNA transcription is repressed in the absence of proper condensin-mediated rDNA condensation, Rad52 readily enters the nucleolus, leading to rDNA instability

Summary

Introduction

In Saccharomyces cerevisiae, there are ϳ150 copies of rDNA tandem repeats on chromosome XII. We observed that inactivation of rDNA transcription by a mutation of RRN3 (which encodes an essential Pol I transcription factor) or RPA190 (which encodes the largest Pol I subunit) leads to nucleolar fragmentation and ERC formation Consistent with these observations, a top1top double mutant shows a substantial inhibition of rRNA synthesis and an unstable rDNA phenotype as revealed by an increased level of ERC [5]. These results suggest that active rDNA transcription has a role in maintaining rDNA stability.

Objectives

Results

Conclusion