| Autor: |
Liang, CC, Li, Z, Lopez-Martinez, D, Nicholson, WV, Vénien-Bryan, C, Cohn, MA |
| Rok vydání: |
2016 |
| Předmět: |
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| DOI: |
10.1038/ncomms12124 |
| Popis: |
The Fanconi Anemia (FA) pathway is important for the repair of DNA interstrand crosslinks (ICL). The FANCD2-FANCI complex is central to the pathway, and localizes to ICLs dependent on its monoubiquitination. It has remained elusive whether the complex is recruited before or after the critical monoubiquitination. Here we report the first structural insight into the human FANCD2-FANCI complex by obtaining the cryo- EM structure. The complex contains an inner cavity, large enough to accommodate a double stranded DNA helix, as well as a protruding Tower domain. Disease-causing mutations in the Tower domain is observed in several FA patients. Our work reveals that recruitment of the complex to a stalled replication fork serves as the trigger for the activating monoubiquitination event. Taken together, our results uncover the mechanism of how the FANCD2-FANCI complex activates the FA pathway, and explains the underlying molecular defect in FA patients with mutations in the Tower domain. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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