Proteomics

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Uncovering Global Non-Covalent SUMO Binder Networks Reveals that Sumoylation enhances XRCC4 activitythe stabilization of the classical Non Homologous End Joining complex.

ABSTRACT: In contrast to our extensive knowledge on covalent SUMO target proteins, we are limited in our understanding of proteins that bind SUMO family members in a non-covalent manner. We have identified interactors of different SUMO isoforms: monomeric SUMO1, monomeric SUMO2 or linear trimeric SUMO2 chains, using a mass spectrometry-based proteomics approach. We identified 382 proteins that bind to different SUMO isoforms mainly in a preferential manner. Interestingly, XRCC4 was 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 functional SIM in XRCC4 regulated its recruitment to local sites of DNA damage and its phosphorylation in S320 by DNA-PKcs. Combined, our data highlight the importance of non-covalent and covalent sumoylation for DNA double-strand break repair via the NHEJ pathway and provides a resource of SUMO isoform interactors.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Román González-Prieto  

LAB HEAD: Alfred C.O. Vertegaal

PROVIDER: PXD022924 | Pride | 2021-01-29

REPOSITORIES: Pride

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

González-Prieto Román R   Eifler-Olivi Karolin K   Claessens Laura A LA   Willemstein Edwin E   Xiao Zhenyu Z   Talavera Ormeno Cami M P CMP   Ovaa Huib H   Ulrich Helle D HD   Vertegaal Alfred C O ACO  

Cell reports 20210101 4

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  ...[more]

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