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, L. Haracska, Serge Gangloff, Lumir Krejci

Research output: Contribution to journalArticle

39 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

Fingerprint

Proliferating Cell Nuclear Antigen
DNA Repair
Repair
DNA
Homologous Recombination
Genes
Switches
Sumoylation
Genomic Instability
DNA Replication
Yeast
Genetic Recombination
DNA Damage
Machinery
Yeasts
Association reactions
Genome

Keywords

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

ASJC Scopus subject areas

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

Cite this

Burkovics, P., Sebesta, M., Sisakova, A., Plault, N., Szukacsov, V., Robert, T., ... 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

Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis. / Burkovics, Peter; Sebesta, Marek; Sisakova, Alexandra; Plault, Nicolas; Szukacsov, Valeria; Robert, Thomas; Pinter, Lajos; Marini, Victoria; Kolesar, Peter; Haracska, L.; Gangloff, Serge; Krejci, Lumir.

In: EMBO Journal, Vol. 32, No. 5, 06.03.2013, p. 742-755.

Research output: Contribution to journalArticle

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, vol. 32, no. 5, pp. 742-755. https://doi.org/10.1038/emboj.2013.9
Burkovics P, Sebesta M, Sisakova A, Plault N, Szukacsov V, Robert T et al. Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis. EMBO Journal. 2013 Mar 6;32(5):742-755. https://doi.org/10.1038/emboj.2013.9
Burkovics, Peter ; Sebesta, Marek ; Sisakova, Alexandra ; Plault, Nicolas ; Szukacsov, Valeria ; Robert, Thomas ; Pinter, Lajos ; Marini, Victoria ; Kolesar, Peter ; Haracska, L. ; Gangloff, Serge ; Krejci, Lumir. / Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis. In: EMBO Journal. 2013 ; Vol. 32, No. 5. pp. 742-755.
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