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

Peter Burkovics, Marek Sebesta, Alexandra Sisakova, Nicolas Plault, Valeria Szukacsov, Thomas Robert, Lajos Pinter, Victoria Marini, Peter Kolesar, Lajos Haracska, Serge Gangloff, Lumir Krejci

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43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)742-755
Number of pages14
JournalEMBO Journal
Volume32
Issue number5
DOIs
Publication statusPublished - Mar 6 2013

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Keywords

  • DNA repair synthesis
  • PCNA SUMOylation
  • SUMO interacting motif
  • Srs2
  • genome stability

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Burkovics, P., Sebesta, M., Sisakova, A., Plault, N., Szukacsov, V., Robert, T., Pinter, L., Marini, V., Kolesar, P., Haracska, L., Gangloff, S., & Krejci, L. (2013). Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis. EMBO Journal, 32(5), 742-755. https://doi.org/10.1038/emboj.2013.9