RNF111-Dependent Neddylation Activates DNA Damage-Induced Ubiquitination

Ubiquitin-like proteins have been shown to be covalently conjugated to targets. However, the functions of these ubiquitin-like proteins are largely unknown. Here, we have screened most known ubiquitin-like proteins after DNA damage and found that NEDD8 is involved in the DNA damage response. Followi...

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Bibliographic Details
Published in:Molecular cell 2013-03, Vol.49 (5), p.897-907
Main Authors: Ma, Teng, Chen, Yibin, Zhang, Feng, Yang, Chao-Yie, Wang, Shaomeng, Yu, Xiaochun
Format: Article
Language:English
Subjects:
BRCA1 protein
BRCA1 Protein - genetics
BRCA1 Protein - metabolism
Cell Line
Cells, Cultured
damage
DNA
DNA - metabolism
DNA Damage
DNA Repair
histones
Histones - metabolism
Humans
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
lysine
NEDD8 Protein
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Polyadenylation
Tumor Suppressor p53-Binding Protein 1
tumor suppressor proteins
ubiquitin
ubiquitin-protein ligase
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
Ubiquitins - genetics
Ubiquitins - metabolism
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Summary:Ubiquitin-like proteins have been shown to be covalently conjugated to targets. However, the functions of these ubiquitin-like proteins are largely unknown. Here, we have screened most known ubiquitin-like proteins after DNA damage and found that NEDD8 is involved in the DNA damage response. Following various DNA damage stimuli, NEDD8 accumulated at DNA damage sites; this accumulation was dependent on an E2 enzyme (UBE2M) and an E3 ubiquitin ligase (RNF111). We further found that histone H4 was polyneddylated in response to DNA damage, and NEDD8 was conjugated to the N-terminal lysine residues of H4. Interestingly, the DNA damage-induced polyneddylation chain could be recognized by the MIU (motif interacting with ubiquitin) domain of RNF168. Loss of DNA damage-induced neddylation negatively regulated DNA damage-induced foci formation of RNF168 and its downstream functional partners, such as 53BP1 and BRCA1, thus affecting the normal DNA damage repair process. ► Histone neddylation is a DNA damage-induced epigenetic modification ► Neddylation regulates DNA damage-induced ubiquitination cascade ► Polyneddylation occurs in response to DNA damage in vivo ► Polyneddylation can be recognized by a ubiquitin-binding motif
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2013.01.006