title: Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis.
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.
authors: National Centre for Biomolecular Research, Masaryk University, Brno, Czech Republic.
authors: Peter
authors: P
authors: Burkovics
authors: Marek
authors: M
authors: Sebesta
authors: Alexandra
authors: A
authors: Sisakova
authors: Nicolas
authors: N
authors: Plault
authors: Valeria
authors: V
authors: Szukacsov
authors: Thomas
authors: T
authors: Robert
authors: Lajos
authors: L
authors: Pinter
authors: Victoria
authors: V
authors: Marini
authors: Peter
authors: P
authors: Kolesar
authors: Lajos
authors: L
authors: Haracska
authors: Serge
authors: S
authors: Gangloff
authors: Lumir
authors: L
authors: Krejci
mesh_terms: D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism; D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D004261:DNA Replication / Q000235:genetics / Q000528:radiation effects; D042822:Genomic Instability; D059765:Homologous Recombination; D009154:Mutation / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; C061376:SRS2 protein, S cerevisiae; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D004265:DNA Helicases
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