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Srs2 mediates PCNA‐SUMO‐dependent inhibition of DNA repair synthesis
Author(s) -
Burkovics Peter,
Sebesta Marek,
Sisakova Alexandra,
Plault Nicolas,
Szukacsov Valeria,
Robert Thomas,
Pinter Lajos,
Marini Victoria,
Kolesar Peter,
Haracska Lajos,
Gangloff Serge,
Krejci Lumir
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.9
Subject(s) - biology , proliferating cell nuclear antigen , rad51 , dna repair , dna mismatch repair , homologous recombination , dna replication , microbiology and biotechnology , genetics , dna
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.