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

Nature Communications
Nam Soo LeeHongtae Kim

Abstract

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.

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Citations

Jul 28, 2016·Cell Discovery·Wanjuan FengMichael Shing-Yan Huen
Nov 29, 2017·Nucleic Acids Research·Jakub A KochanPrzemek M Krawczyk
Apr 14, 2019·Life Science Alliance·Sara Priego MorenoAgnieszka Gambus
Jul 7, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Patrick M LombardiCynthia Wolberger
Sep 28, 2018·International Journal of Molecular Sciences·Maïlyn Yates, Alexandre Maréchal
May 1, 2020·Nature Communications·Li Ren KongBoon Cher Goh
Dec 16, 2020·Trends in Cell Biology·R Alex WuJohannes C Walter
Jun 13, 2020·Trends in Cancer·Yuwen LiGuoyu Meng
May 9, 2021·Nucleic Acids Research·Min Kyung JuYoung Chan Chae
Aug 20, 2021·Nature Communications·John J KraisNeil Johnson

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Methods Mentioned

BETA
ubiquitination
two-hybrid
immunoprecipitation
co-immunoprecipitation
pulldown
immunoprecipitation assay
transfection
flow cytometry
confocal microscopy

Software Mentioned

Prism
NIS elements C
GraphPad

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