TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage

RAP80 localizes to sites of DNA insults to enhance the DNA-damage responses. Here we identify TRAIP/RNF206 as a novel RAP80-interacting protein and find that TRAIP is necessary for translocation of RAP80 to DNA lesions. Depletion of TRAIP results in impaired accumulation of RAP80 and functional down...

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Detalles Bibliográficos
Autores principales: Soo Lee, Nam, Jin Chung, Hee, Kim, Hyoung-June, Yun Lee, Seo, Ji, Jae-Hoon, Seo, Yoojeong, Hun Han, Seung, Choi, Minji, Yun, Miyong, Lee, Seok-Geun, Myung, Kyungjae, Kim, Yonghwan, Chul Kang, Ho, Kim, Hongtae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735692/
https://www.ncbi.nlm.nih.gov/pubmed/26781088
http://dx.doi.org/10.1038/ncomms10463
Descripción
Sumario:RAP80 localizes to sites of DNA insults to enhance the DNA-damage responses. Here we identify TRAIP/RNF206 as a novel RAP80-interacting protein and find that TRAIP is necessary for translocation of RAP80 to DNA lesions. Depletion of TRAIP results in impaired accumulation of RAP80 and functional downstream partners, including BRCA1, at DNA lesions. Conversely, accumulation of TRAIP is normal in RAP80-depleted cells, implying that TRAIP acts upstream of RAP80 recruitment to DNA lesions. TRAIP localizes to sites of DNA damage and cells lacking TRAIP exhibit classical DNA-damage response-defect phenotypes. Biochemical analysis reveals that the N terminus of TRAIP is crucial for RAP80 interaction, while the C terminus of TRAIP is required for TRAIP localization to sites of DNA damage through a direct interaction with RNF20–RNF40. Taken together, our findings demonstrate that the novel RAP80-binding partner TRAIP regulates recruitment of the damage signalling machinery and promotes homologous recombination.