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RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO

Author

Listed:
  • Carsten Hoege

    (Max Planck Institute of Biochemistry)

  • Boris Pfander

    (Max Planck Institute of Biochemistry)

  • George-Lucian Moldovan

    (Max Planck Institute of Biochemistry)

  • George Pyrowolakis

    (Max Planck Institute of Biochemistry
    Biocenter, University of Basel)

  • Stefan Jentsch

    (Max Planck Institute of Biochemistry)

Abstract

The RAD6 pathway is central to post-replicative DNA repair in eukaryotic cells; however, the machinery and its regulation remain poorly understood. Two principal elements of this pathway are the ubiquitin-conjugating enzymes RAD6 and the MMS2–UBC13 heterodimer, which are recruited to chromatin by the RING-finger proteins RAD18 and RAD5, respectively. Here we show that UBC9, a small ubiquitin-related modifier (SUMO)-conjugating enzyme, is also affiliated with this pathway and that proliferating cell nuclear antigen (PCNA)—a DNA-polymerase sliding clamp involved in DNA synthesis and repair—is a substrate. PCNA is mono-ubiquitinated through RAD6 and RAD18, modified by lysine-63-linked multi-ubiquitination—which additionally requires MMS2, UBC13 and RAD5—and is conjugated to SUMO by UBC9. All three modifications affect the same lysine residue of PCNA, suggesting that they label PCNA for alternative functions. We demonstrate that these modifications differentially affect resistance to DNA damage, and that damage-induced PCNA ubiquitination is elementary for DNA repair and occurs at the same conserved residue in yeast and humans.

Suggested Citation

  • Carsten Hoege & Boris Pfander & George-Lucian Moldovan & George Pyrowolakis & Stefan Jentsch, 2002. "RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO," Nature, Nature, vol. 419(6903), pages 135-141, September.
    • Handle: RePEc:nat:nature:v:419:y:2002:i:6903:d:10.1038_nature00991
    DOI: 10.1038/nature00991
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    Cited by:

    1. Melissa S Gildenberg & M Todd Washington, 2019. "Conformational flexibility of fork-remodeling helicase Rad5 shown by full-ensemble hybrid methods," PLOS ONE, Public Library of Science, vol. 14(10), pages 1-16, October.

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