Crosstalk Between SUMO and Ubiquitin on PCNA Is Mediated by Recruitment of the Helicase Srs2p

Mol Cell. 2005 Jul 1;19(1):123-33. doi: 10.1016/j.molcel.2005.06.001.

Abstract

Posttranslational modification of proliferating cell nuclear antigen (PCNA), an essential processivity clamp for DNA polymerases, by ubiquitin and SUMO contributes to the coordination of DNA replication, damage tolerance, and mutagenesis. Whereas ubiquitination in response to DNA damage promotes the bypass of replication-blocking lesions, sumoylation during S phase is damage independent. As both modifiers target the same site on PCNA, an antagonistic action of SUMO on ubiquitin-dependent DNA damage tolerance has been proposed. We now present evidence that the apparent negative effect of SUMO on lesion bypass is not due to competition with ubiquitination but is rather mediated by the helicase Srs2p, which affects genome stability by suppressing unscheduled homologous recombination. We show that Srs2p physically interacts with sumoylated PCNA, which contributes to the recruitment of the helicase to replication forks. Our findings suggest a mechanism by which SUMO and ubiquitin cooperatively control the choice of pathway for the processing of DNA lesions during replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromatin Immunoprecipitation
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Glutathione Transferase / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Protein Processing, Post-Translational*
  • Recombinant Fusion Proteins / metabolism
  • SUMO-1 Protein / genetics
  • SUMO-1 Protein / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin / metabolism*

Substances

  • Proliferating Cell Nuclear Antigen
  • Recombinant Fusion Proteins
  • SUMO-1 Protein
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • SRS2 protein, S cerevisiae
  • Glutathione Transferase
  • DNA Helicases