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USP11 Is a Negative Regulator to γH2AX Ubiquitylation by RNF8/RNF168
| Content Provider | Scilit |
|---|---|
| Author | Yu, Miao Liu, Kun Mao, Zebin Luo, Jianyuan Gu, Wei Zhao, Wenhui |
| Copyright Year | 2016 |
| Description | Journal: Journal of Biological Chemistry Ubiquitin modification at double strand breaks (DSB) sites is an essential regulator of signaling and repair. γH2AX extends from DSB sites and provides a platform for subsequent recruitment and amplification of DNA repair proteins and signaling factors. Here, we found that RNF8/RNF168 ubiquitylates γH2AX. We identified that USP11 is a unique deubiquitylation enzyme for γH2AX. USP11 deubiquitylates γH2AX both in vivo and in vitro but not the canonical (ub)-K119-H2A and (ub)-K120-H2B in vitro, and USP11 ablation enhances the levels of γH2AX ubiquitylation. We also found that USP11 interacts with γH2AX both in vivo and in vitro. We found that 53BP1 and ubiquitin-conjugated proteins are misregulated to be retained longer and stronger at DSB sites after knockdown of USP11. We further found that cells are hypersensitive to γ-irradiation after ablation of USP11. Together, our findings elucidate deeply and extensively the mechanism of RNF8/RNF168 and USP11 to maintain the proper status of ubiquitylation γH2AX to repair DSB. |
| Related Links | http://www.jbc.org/content/291/2/959.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705413/pdf http://www.jbc.org/article/S0021925820362268/pdf |
| Ending Page | 967 |
| Page Count | 9 |
| Starting Page | 959 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m114.624478 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 2 |
| Volume Number | 291 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2016-01-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Cell Biology E3 Ubiquitin-protein Ligase Rnf8 (rnf8) H2a Histone Family, Member X (h2afx) Deubiquitylation (deubiquitination) Ubiquitin-dependent Protease Ubiquitylation (ubiquitination) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |