RNF4 ubiquitinates MDC1

Stable Identifier
R-HSA-5684071
Type
Reaction [transition]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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RNF4 ubiquitinates MDC1
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SUMOylation of MDC1 by PIAS4 creates a docking site for RNF4, an E3 ubiquitin ligase. RNF4 binds to MDC1 specifically when SUMO2 is attached to lysine K1840 of MDC1. RNF4 polyubiquitinates MDC1 through ubiquitin lysine residue K48 cross-linking. RNF4-mediated ubiquitination targets MDC1 for degradation and causes dissociation of MDC1-bound proteins from DNA double-strand breaks (DSBs). While additional regulation steps may be involved, the activity of RNF4 is necessary for the initiation of resection of DNA ends at DSBs and progression of homologous recombination (Luo et al. 2012, Yin et al. 2012, Galanty et al. 2012).
Literature References
PubMed ID Title Journal Year
22661230 SUMO-targeted ubiquitin E3 ligase RNF4 is required for the response of human cells to DNA damage

Yin, Y, Seifert, A, Chua, JS, Maure, JF, Golebiowski, F, Hay, RT

Genes Dev. 2012
22661229 RNF4, a SUMO-targeted ubiquitin E3 ligase, promotes DNA double-strand break repair

Galanty, Y, Belotserkovskaya, R, Coates, J, Jackson, SP

Genes Dev. 2012
22635276 Sumoylation of MDC1 is important for proper DNA damage response

Luo, K, Zhang, H, Wang, L, Yuan, J, Lou, Z

EMBO J. 2012
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Catalyst Activity

ubiquitin protein ligase activity of RNF4 homodimer [nucleoplasm]

Physical Entity
RNF4 homodimer [nucleoplasm] (Homo sapiens)
Activity
ubiquitin protein ligase activity (GO:0061630)
Orthologous Events
RNF4 ubiquitinates MDC1 (Bos taurus)
RNF4 ubiquitinates MDC1 (Mus musculus)
Authored
Orlic-Milacic, M  (2015-05-12)
Reviewed
Borowiec, JA  (2015-06-12)
Created
Orlic-Milacic, M  (2015-03-19)
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