Regulation of rDNA stability by sumoylation

Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
DNA Repair (Impact Factor: 3.11). 05/2009; 8(4):507-16. DOI: 10.1016/j.dnarep.2009.01.015
Source: PubMed


Repair of DNA lesions by homologous recombination relies on the copying of genetic information from an intact homologous sequence. However, many eukaryotic genomes contain repetitive sequences such as the ribosomal gene locus (rDNA), which poses a risk for illegitimate recombination. Therefore, the eukaryotic cell has evolved mechanisms to favor equal sister chromatid exchange (SCE) and suppress unequal SCE, single-strand annealing and break-induced replication. In the budding yeast Saccharomyces cerevisiae, the tight regulation of homologous recombination at the rDNA locus is dependent on the Smc5-Smc6 complex and sumoylation of Rad52, which directs DNA double-strand breaks in the rDNA to relocalize from within the nucleolus to the nucleoplasm before association with the recombination machinery. The relocalization before repair is important for maintaining rDNA stability. The focus of this review is the regulation of recombinational DNA repair at the rDNA locus by sumoylation and the Smc5-Smc6 complex in S. cerevisiae.

26 Reads
  • Source
    • "Post-translational protein modifications with SUMO1 and SUMO2/3 are well known to have multiple roles, such as regulating protein activity, stability and/or subcellular localisation, and have also been linked to rDNA maintenance (reviewed in Eckert-Boulet and Lisby (2009) and Geiss-Friedlander and Melchior (2007)). We recently reported a proteomic screen for SUMOylated proteins within the nucleolus, demonstrating a role for SUMOylation of Nop5/Nop58 in the regulation for snoRNP biogenesis (Westman et al. 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The nucleolus is the subnuclear organelle responsible for ribosome subunit biogenesis and can also act as a stress sensor. It forms around clusters of ribosomal DNA (rDNA) and is mainly organised in three subcompartments, i.e. fibrillar centre, dense fibrillar component and granular component. Here, we describe the localisation of 21 protein factors to an intranucleolar region different to these main subcompartments, called the intranucleolar body (INB). These factors include proteins involved in DNA maintenance, protein turnover, RNA metabolism, chromatin organisation and the post-translational modifiers SUMO1 and SUMO2/3. Increase in the size and number of INBs is promoted by specific types of DNA damage and depends on the functional integrity of the nucleolus. INBs are abundant in nucleoli of unstressed cells during S phase and localise in close proximity to rDNA with heterochromatic features. The data suggest the INB is linked with regulation of rDNA transcription and/or maintenance of rDNA. Electronic supplementary material The online version of this article (doi:10.1007/s00412-011-0327-8) contains supplementary material, which is available to authorized users.
    Full-text · Article · Jun 2011 · Chromosoma
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: All cells of human organism are continuously damaged, and a damage of the genetic material can be especially dangerous. The reaction of the cell to DNA damage is a complex process, which includes damage signaling, repair, apoptosis or cell death. It is connected with serious changes in the cell nucleus, which are caused by posttranslational modifications and dynamic relocalizations of proteins as well as alterations in the expression of many genes. These changes are not limited to the sites of DNA damage, but involve whole cell nucleus, including its domains: PML bodies, nucleolus and Cajal bodies.
    Full-text · Article · Jan 2010 · Postepy biochemii
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Posttranslational SUMO modification is an important mechanism of regulating protein function, especially in the cell nucleus. The nucleolus is the subnuclear organelle responsible for rRNA synthesis, processing, and assembly of the large and small ribosome subunits. Here, we have used SILAC-based quantitative proteomics to identify nucleolar SUMOylated proteins. This reveals a role for SUMOylation in the biogenesis and/or function of small nucleolar ribonucleoprotein complexes (snoRNPs) via the targeting of Nhp2 and Nop58. Using combined in vitro and in vivo approaches, both Nhp2 and Nop58 (also known as Nop5) are shown to be substrates for SUMOylation. Mutational analyses revealed the sites of modification on Nhp2 as K5, and on Nop58 as K467 and K497. Unlike Nop58 and Nhp2, the closely related Nop56 and 15.5K proteins appear not to be SUMO targets. SUMOylation is essential for high-affinity Nop58 binding to snoRNAs. This study provides direct evidence linking SUMO modification with snoRNP function.
    Full-text · Article · Aug 2010 · Molecular cell
Show more