Abstract

Homologous recombination (HR) is crucial for maintaining genome integrity by repairing DNA double-strand breaks (DSBs) and rescuing collapsed replication forks. In contrast, uncontrolled HR can lead to chromosome translocations, loss of heterozygosity, and deletion of repetitive sequences. Controlled HR is particularly important for the preservation of repetitive sequences of the ribosomal gene (rDNA) cluster. Here we show that recombinational repair of a DSB in rDNA in Saccharomyces cerevisiae involves the transient relocalization of the lesion to associate with the recombination machinery at an extranucleolar site. The nucleolar exclusion of Rad52 recombination foci entails Mre11 and Smc5–Smc6 complexes and depends on Rad52 SUMO (small ubiquitin-related modifier) modification. Remarkably, mutations that abrogate these activities result in the formation of Rad52 foci within the nucleolus and cause rDNA hyperrecombination and the excision of extrachromosomal rDNA circles. Our study also suggests a key role of sumoylation for nucleolar dynamics, perhaps in the compartmentalization of nuclear activities.

1. Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
2. Department of Genetics & Development, Columbia University Medical Center, 701 West 168th Street, New York, New York 10032-2704, USA.
3. Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
4. Department of Molecular Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
5. Current address: Departament de Ciències Mèdiques Bàsiques, IRBLLEIDA, Universitat de Lleida, C/ Montserrat Roig 2, 25008 Lleida, Spain.
6. These authors contributed equally to this work.

Correspondence to: Michael Lisby⁴ e-mail: mlisby@my.molbio.ku.dk

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