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SUMOylation regulates Rad18-mediated template switch

Author

Listed:
  • Dana Branzei

    (IFOM, the FIRC Institute for Molecular Oncology Foundation, IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy)

  • Fabio Vanoli

    (IFOM, the FIRC Institute for Molecular Oncology Foundation, IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy)

  • Marco Foiani

    (IFOM, the FIRC Institute for Molecular Oncology Foundation, IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy
    Università degli Studi di Milano)

Abstract

Replication by template switch is thought to mediate DNA damage-bypass and fillings of gaps. Gap-filling repair requires homologous recombination as well as Rad18- and Rad5-mediated proliferating cell nuclear antigen (PCNA) polyubiquitylation. However, it is unclear whether these processes are coordinated, and the physical evidence for Rad18–Rad5-dependent template switch at replication forks is still elusive. Here we show, using genetic and physical approaches, that in budding yeast (Saccharomyces cerevisiae) Rad18 is required for the formation of X-shaped sister chromatid junctions (SCJs) at damaged replication forks through a process involving PCNA polyubiquitylation and the ubiquitin-conjugating enzymes Mms2 and Ubc13. The Rad18–Mms2-mediated damage-bypass through SCJs requires the small ubiquitin-like modifier (SUMO)-conjugating enzyme Ubc9 and SUMOylated PCNA, and is coordinated with Rad51-dependent recombination events. We propose that the Rad18–Rad5–Mms2-dependent SCJs represent template switch events. Altogether, our results unmask a role for PCNA ubiquitylation and SUMOylation pathways in promoting transient damage-induced replication-coupled recombination events involving sister chromatids at replication forks.

Suggested Citation

  • Dana Branzei & Fabio Vanoli & Marco Foiani, 2008. "SUMOylation regulates Rad18-mediated template switch," Nature, Nature, vol. 456(7224), pages 915-920, December.
    • Handle: RePEc:nat:nature:v:456:y:2008:i:7224:d:10.1038_nature07587
    DOI: 10.1038/nature07587
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    Cited by:

    1. Nagham Ghaddar & Yves Corda & Pierre Luciano & Martina Galli & Ylli Doksani & Vincent Géli, 2023. "The COMPASS subunit Spp1 protects nascent DNA at the Tus/Ter replication fork barrier by limiting DNA availability to nucleases," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Chinnu Rose Joseph & Sabrina Dusi & Michele Giannattasio & Dana Branzei, 2022. "Rad51-mediated replication of damaged templates relies on monoSUMOylated DDK kinase," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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