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

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.
Mesh Terms:
DNA Damage, DNA Helicases, DNA Polymerase II, DNA Polymerase III, DNA Repair, DNA Replication, Genomic Instability, Homologous Recombination, Mutation, Proliferating Cell Nuclear Antigen, Rad51 Recombinase, SUMO-1 Protein, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sumoylation, Ultraviolet Rays
EMBO J.
Date: Mar. 06, 2013
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