title: RNF111-dependent neddylation activates DNA damage-induced ubiquitination.
abstract: 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.
authors: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Teng
authors: T
authors: Ma
authors: Yibin
authors: Y
authors: Chen
authors: Feng
authors: F
authors: Zhang
authors: Chao-Yie
authors: CY
authors: Yang
authors: Shaomeng
authors: S
authors: Wang
authors: Xiaochun
authors: X
authors: Yu
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000075687:NEDD8 Protein; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D026723:Polyadenylation; D000071857:Tumor Suppressor p53-Binding Protein 1; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D009687:Nuclear Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D014452:Ubiquitins; D004247:DNA; C486067:RNF111 protein, human; D044767:Ubiquitin-Protein Ligases
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