論文 - 詳細
| RRC ID | 82837 |
|---|---|
| 著者 | Katsuki Y, Abe M, Park SY, Wu W, Yabe H, Yabe M, van Attikum H, Nakada S, Ohta T, Seidman MM, Kim Y, Takata M. |
| タイトル | RNF168 E3 ligase participates in ubiquitin signaling and recruitment of SLX4 during DNA crosslink repair. |
| ジャーナル | Cell Rep |
| Abstract |
SLX4/FANCP is a key Fanconi anemia (FA) protein and a DNA repair scaffold for incision around a DNA interstrand crosslink (ICL) by its partner XPF nuclease. The tandem UBZ4 ubiquitin-binding domains of SLX4 are critical for the recruitment of SLX4 to damage sites, likely by binding to K63-linked polyubiquitin chains. However, the identity of the ubiquitin E3 ligase that mediates SLX4 recruitment remains unknown. Using small interfering RNA (siRNA) screening with a GFP-tagged N-terminal half of SLX4 (termed SLX4-N), we identify the RNF168 E3 ligase as a critical factor for mitomycin C (MMC)-induced SLX4 foci formation. RNF168 and GFP-SLX4-N colocalize in MMC-induced ubiquitin foci. Accumulation of SLX4-N at psoralen-laser ICL tracks or of endogenous SLX4 at Digoxigenin-psoralen/UVA ICL is dependent on RNF168. Finally, we find that RNF168 is epistatic with SLX4 in promoting MMC tolerance. We conclude that RNF168 is a critical component of the signal transduction that recruits SLX4 to ICL damage. |
| 巻・号 | 37(4) |
| ページ | 109879 |
| 公開日 | 2021-10-26 |
| DOI | 10.1016/j.celrep.2021.109879 |
| PII | S2211-1247(21)01349-8 |
| PMID | 34706224 |
| PMC | PMC11388903 |
| MeSH | DNA Repair* Digoxigenin / pharmacology Ficusin / pharmacology HCT116 Cells Humans MCF-7 Cells Mitomycin / pharmacology Recombinases / genetics Recombinases / metabolism* Signal Transduction* Ubiquitin / genetics Ubiquitin / metabolism* Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* |
| IF | 8.109 |
| リソース情報 | |
| 遺伝子材料 | CSII-CMV-MCS-IRES2-Bsd (RDB04385) |