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

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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

Name	UniProt ID
Protein PML	P29590	Details
Heterogeneous nuclear ribonucleoprotein L	P14866	Details
Stress-induced-phosphoprotein 1	P31948	Details
Hepatoma-derived growth factor	P51858	Details
Ran-specific GTPase-activating protein	P43487	Details
Heterogeneous nuclear ribonucleoprotein F	P52597	Details
Proliferating cell nuclear antigen	P12004	Details
Chromobox protein homolog 5	P45973	Details
Filamin-A	P21333	Details
Nucleophosmin	P06748	Details
Small nuclear ribonucleoprotein Sm D2	P62316	Details
Probable ATP-dependent RNA helicase DDX5	P17844	Details
Proliferation marker protein Ki-67	P46013	Details