SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage.

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Hendriks IA, Treffers LW, Verlaan-de Vries M, Olsen JV, Vertegaal AC

SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage.

Cell Rep. 2015 Mar 10. pii: S2211-1247(15)00179-5. doi: 10.1016/j.celrep.2015.02.033.

PubMed ID
25772364 [ View in PubMed
]
Abstract

Small ubiquitin-like modifiers play critical roles in the DNA damage response (DDR). To increase our understanding of SUMOylation in the mammalian DDR, we employed a quantitative proteomics approach in order to identify dynamically regulated SUMO-2 conjugates and modification sites upon treatment with the DNA damaging agent methyl methanesulfonate (MMS). We have uncovered a dynamic set of 20 upregulated and 33 downregulated SUMO-2 conjugates, and 755 SUMO-2 sites, of which 362 were dynamic in response to MMS. In contrast to yeast, where a response is centered on homologous recombination, we identified dynamically SUMOylated interaction networks of chromatin modifiers, transcription factors, DNA repair factors, and nuclear body components. SUMOylated chromatin modifiers include JARID1B/KDM5B, JARID1C/KDM5C, p300, CBP, PARP1, SetDB1, and MBD1. Whereas SUMOylated JARID1B was ubiquitylated by the SUMO-targeted ubiquitin ligase RNF4 and degraded by the proteasome in response to DNA damage, JARID1C was SUMOylated and recruited to the chromatin to demethylate histone H3K4.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Protein PMLP29590Details
Heterogeneous nuclear ribonucleoprotein LP14866Details
Stress-induced-phosphoprotein 1P31948Details
Hepatoma-derived growth factorP51858Details
Ran-specific GTPase-activating proteinP43487Details
Heterogeneous nuclear ribonucleoprotein FP52597Details
Proliferating cell nuclear antigenP12004Details
Chromobox protein homolog 5P45973Details
Filamin-AP21333Details
NucleophosminP06748Details
Small nuclear ribonucleoprotein Sm D2P62316Details
Probable ATP-dependent RNA helicase DDX5P17844Details
Proliferation marker protein Ki-67P46013Details