Global non-covalent SUMO interaction networks reveal SUMO-dependent stabilization of the non-homologous end joining complex

Cell Rep. 2021 Jan 26;34(4):108691. doi: 10.1016/j.celrep.2021.108691.

Abstract

In contrast to our extensive knowledge on covalent small ubiquitin-like modifier (SUMO) target proteins, we are limited in our understanding of non-covalent SUMO-binding proteins. We identify interactors of different SUMO isoforms-monomeric SUMO1, monomeric SUMO2, or linear trimeric SUMO2 chains-using a mass spectrometry-based proteomics approach. We identify 379 proteins that bind to different SUMO isoforms, mainly in a preferential manner. Interestingly, XRCC4 is the only DNA repair protein in our screen with a preference for SUMO2 trimers over mono-SUMO2, as well as the only protein in our screen that belongs to the non-homologous end joining (NHEJ) DNA double-strand break repair pathway. A SUMO interaction motif (SIM) in XRCC4 regulates its recruitment to sites of DNA damage and phosphorylation of S320 by DNA-PKcs. Our data highlight the importance of non-covalent and covalent sumoylation for DNA double-strand break repair via the NHEJ pathway and provide a resource of SUMO isoform interactors.

Keywords: DNA damage response; SUMO; SUMO Interaction Motif; SUMO1; SUMO2; chain; mass spectrometry; non-homologous end joining; small ubiquitin-like modifier; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA End-Joining Repair / genetics*
  • DNA Repair / genetics*
  • Humans
  • Protein Binding / genetics*
  • SUMO-1 Protein / metabolism*

Substances

  • SUMO-1 Protein
  • SUMO1 protein, human