Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks
| Autor: | Ho Lee, Chang-Woo Lee, Jeong-Min Park, Sunyoung Chae, Hyeseong Cho, Tae-Hong Kang, Sunwoo Min, Jihyun Park, Jae-Hoon Ji, Suhyeon Kim, Jin-Kwan Lee, Geun-Hyoung Ha, Y. C. Kim |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
DNA Repair DNA damage DNA repair Science Ubiquitin-Protein Ligases genetic processes General Physics and Astronomy Cell Cycle Proteins 02 engineering and technology Ataxia Telangiectasia Mutated Proteins General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound Ubiquitin Cell Line Tumor Humans DNA Breaks Double-Stranded lcsh:Science Phosphorylated Histone H2AX Multidisciplinary biology fungi Ubiquitination Nuclear Proteins General Chemistry 021001 nanoscience & nanotechnology Cell biology Ubiquitin ligase enzymes and coenzymes (carbohydrates) 030104 developmental biology chemistry biology.protein health occupations Phosphorylation lcsh:Q biological phenomena cell phenomena and immunity 0210 nano-technology Homologous recombination DNA |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-18 (2019) |
| ISSN: | 2041-1723 |
| Popis: | DNA double-strand break (DSB) signaling and repair are critical for genome integrity. They rely on highly coordinated processes including posttranslational modifications of proteins. Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. Peli1 is activated by ATM-mediated phosphorylation. It is recruited to DSB sites in ATM- and γH2AX-dependent manners. Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. Collectively, these results provide a DSB-responsive factor underlying the connection between ATM kinase and DSB-induced ubiquitination. Occurrence of DNA double-strand break (DSB) repair is important for genome integrity. Here, the authors reveal that Pellino1 is a DSB-responsive ubiquitin ligase required for promoting the accumulation of ATM and MRN complex at DSB sites via NBS1 ubiquitination. |
| Databáze: | OpenAIRE |
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