RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response

J Cell Biol. 2013 Jun 10;201(6):797-807. doi: 10.1083/jcb.201212075.


Protein modifications by ubiquitin and small ubiquitin-like modifier (SUMO) play key roles in cellular signaling pathways. SUMO-targeted ubiquitin ligases (STUbLs) directly couple these modifications by selectively recognizing SUMOylated target proteins through SUMO-interacting motifs (SIMs), promoting their K48-linked ubiquitylation and degradation. Only a single mammalian STUbL, RNF4, has been identified. We show that human RNF111/Arkadia is a new STUbL, which used three adjacent SIMs for specific recognition of poly-SUMO2/3 chains, and used Ubc13-Mms2 as a cognate E2 enzyme to promote nonproteolytic, K63-linked ubiquitylation of SUMOylated target proteins. We demonstrate that RNF111 promoted ubiquitylation of SUMOylated XPC (xeroderma pigmentosum C) protein, a central DNA damage recognition factor in nucleotide excision repair (NER) extensively regulated by ultraviolet (UV)-induced SUMOylation and ubiquitylation. Moreover, we show that RNF111 facilitated NER by regulating the recruitment of XPC to UV-damaged DNA. Our findings establish RNF111 as a new STUbL that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Transformed
  • DNA Damage / physiology
  • DNA Repair / physiology*
  • HeLa Cells
  • Humans
  • Ligases / genetics
  • Ligases / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Plasmids / genetics
  • RNA, Small Interfering / genetics
  • Signal Transduction / physiology
  • Signal Transduction / radiation effects
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Sumoylation / physiology*
  • Sumoylation / radiation effects
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination / physiology
  • Ubiquitination / radiation effects
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*
  • Ultraviolet Rays / adverse effects


  • Nuclear Proteins
  • RNA, Small Interfering
  • SUMO2 protein, human
  • SUMO3 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitins
  • UBE2N protein, human
  • UBE2V2 protein, human
  • Ubiquitin-Conjugating Enzymes
  • RNF111 protein, human
  • Ubiquitin-Protein Ligases
  • Ligases