Ring finger protein RNF169 antagonizes the ubiquitin-dependent signaling cascade at sites of DNA damage.
Ubiquitin signals emanating from DNA double-strand breaks (DSBs) trigger the ordered assembly of DNA damage mediator and repair proteins. This highly orchestrated process is accomplished, in part, through the concerted action of the RNF8 and RNF168 E3 ligases, which have emerged as core signaling intermediates that promote DSB-associated ubiquitylation events. In this study, we report the identification of RNF169 as a negative regulator of the DNA damage signaling cascade. We found that RNF169 interacted with ubiquitin structures and relocalized to DSBs in an RNF8/RNF168-dependent manner. Moreover, ectopic expression of RNF169 attenuated ubiquitin signaling and compromised 53BP1 accumulation at DNA damage sites, suggesting that RNF169 antagonizes RNF168 functions at DSBs. Our study unveils RNF169 as a component in DNA damage signal transduction and adds to the complexity of regulatory ubiquitylation in genome stability maintenance.
Genome Stability Research Laboratory, The University of Hong Kong, Hong Kong, China.
Jie
J
Chen
Wanjuan
W
Feng
Jun
J
Jiang
Yiqun
Y
Deng
Michael S Y
MS
Huen
D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D015398:Signal Transduction; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D004268:DNA-Binding Proteins; C486521:RNF8 protein, human; D025801:Ubiquitin; C572547:RNF169 protein, human; D044767:Ubiquitin-Protein Ligases