Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis

• Peter Burkovics ^[7] ; Marek Sebesta ^[4] ; Alexandra Sisakova ^[1] ; Nicolas Plault ^[2] ; Valeria Szukacsov ^[3] ; Thomas Robert ^[2] ; Lajos Pinter ^[3] ; Victoria Marini ^[1] ; Peter Kolesar ^[4] ; Lajos Haracska ^[3] ; Serge Gangloff ^[5] ; Lumir Krejci ^[6]
  1. [1] Masaryk University

     Masaryk University

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  2. [2] CEA, DSV, IRCM, SIGRR, LERA, Fontenay-aux-Roses, France
  3. [3] Biological Research Center, Institute of Genetics, Hungarian Academy of Sciences, Szeged, Hungary
  4. [4] National Centre for Biomolecular Research, Masaryk University, Brno, Czech Republic; Department of Biology, Masaryk University, Brno, Czech Republic
  5. [5] CEA, DSV, IRCM, SIGRR, LERA, Fontenay-aux-Roses, France; CNRS, UMR 217, Fontenay-aux-Roses, France
  6. [6] National Centre for Biomolecular Research, Masaryk University, Brno, Czech Republic; Department of Biology, Masaryk University, Brno, Czech Republic; International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, Brno, Czech Republic
  7. [7] National Centre for Biomolecular Research, Masaryk University, Brno, Czech Republic; Biological Research Center, Institute of Genetics, Hungarian Academy of Sciences, Szeged, Hungary

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 32, Nº. 5, 2013, págs. 742-755
• Idioma: inglés
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  • Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Polδ and Polη from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability.