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

Burkovics, Péter and Sebesta, Marek and Sisakova, Alexandra and Szukacsov, Valéria and Pintér, Lajos and Haracska, Lajos (2013) Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis. EMBO JOURNAL, 32 (5). pp. 742-755. ISSN 0261-4189

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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. © 2013 European Molecular Biology Organization.

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