The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus.

TY - JOUR

T1 - The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus.

AU - Torres-Rosell, Jordi

AU - Sunjevaric, Ivana

AU - De Piccoli, Giacomo

AU - Sacher, Meik

AU - Eckert-Boulet, Nadine

AU - Reid, Robert

AU - Jentsch, Stefan

AU - Rothstein, Rodney

AU - Aragón, Luis

AU - Lisby, Michael

N1 - Keywords: Cell Cycle Proteins; Cell Nucleolus; DNA Damage; DNA Repair; DNA, Ribosomal; Rad52 DNA Repair and Recombination Protein; Recombination, Genetic; Ribosomes; SUMO-1 Protein; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

U2 - 10.1038/ncb1619

DO - 10.1038/ncb1619

M3 - Journal article

C2 - 17643116

SN - 1465-7392

VL - 9

SP - 923

EP - 931

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 8

ER -