The EMBO journal, 2013-03, Vol.32 (5), p.742-755
2013
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Srs2 mediates PCNA‐SUMO‐dependent inhibition of DNA repair synthesis
- Ist Teil von
- The EMBO journal, 2013-03, Vol.32 (5), p.742-755
- Ort / Verlag
- Chichester, UK: John Wiley & Sons, Ltd
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. An unexpected non‐catalytic function of the recombination‐attenuating helicase Srs2 further expands the manifold roles of PCNA modifications in ensuring genome stability.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0261-4189eISSN: 1460-2075DOI: 10.1038/emboj.2013.9Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3594751
- Format
- –
- Schlagworte
- Biochemistry, Molecular Biology, Cell cycle, DNA Damage - genetics, DNA Damage - radiation effects, DNA Helicases - genetics, DNA Helicases - metabolism, DNA Polymerase II - genetics, DNA Polymerase II - metabolism, DNA Polymerase III - genetics, DNA Polymerase III - metabolism, DNA repair, DNA Repair - genetics, DNA Repair - radiation effects, DNA repair synthesis, DNA Replication - genetics, DNA Replication - radiation effects, Genetic recombination, genome stability, Genomic Instability, Homologous Recombination, Life Sciences, Molecular biology, Mutation - genetics, PCNA SUMOylation, Proliferating Cell Nuclear Antigen - genetics, Proliferating Cell Nuclear Antigen - metabolism, Rad51 Recombinase - genetics, Rad51 Recombinase - metabolism, Saccharomyces cerevisiae - genetics, Saccharomyces cerevisiae - metabolism, Saccharomyces cerevisiae Proteins - genetics, Saccharomyces cerevisiae Proteins - metabolism, Srs2, SUMO interacting motif, SUMO-1 Protein - genetics, SUMO-1 Protein - metabolism, Sumoylation, Ultraviolet Rays - adverse effects