RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response

EMBO Rep. 2014 May;15(5):601-8. doi: 10.1002/embr.201338369. Epub 2014 Apr 8.

Abstract

The post-translational modification of DNA repair and checkpoint proteins by ubiquitin and small ubiquitin-like modifier (SUMO) critically orchestrates the DNA damage response (DDR). The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin, through its selective recognition and ubiquitination of SUMO-modified proteins. Here, we define a key new determinant for target discrimination by RNF4, in addition to interaction with SUMO. We identify a nucleosome-targeting motif within the RNF4 RING domain that can bind DNA and thereby enables RNF4 to selectively ubiquitinate nucleosomal histones. Furthermore, RNF4 nucleosome-targeting is crucially required for the repair of TRF2-depleted dysfunctional telomeres by 53BP1-mediated non-homologous end joining.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cell Line
  • Chromosomal Proteins, Non-Histone / metabolism
  • Crystallography, X-Ray
  • DNA Damage
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • Gene Knockout Techniques
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / ultrastructure*
  • Nucleosomes / metabolism*
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology
  • Telomere / drug effects
  • Telomere / genetics
  • Telomeric Repeat Binding Protein 2 / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors / ultrastructure*
  • Tumor Suppressor p53-Binding Protein 1
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases
  • Ubiquitination

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Nucleosomes
  • Small Ubiquitin-Related Modifier Proteins
  • TRF2 protein, mouse
  • Telomeric Repeat Binding Protein 2
  • Transcription Factors
  • Trp53bp1 protein, mouse
  • Tumor Suppressor p53-Binding Protein 1
  • Ubiquitin
  • Tamoxifen
  • afimoxifene
  • Rnf4 protein, mouse
  • Ubiquitin-Protein Ligases