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-Structure paper
タイトル | FANCD2-FANCI is a clamp stabilized on DNA by monoubiquitination of FANCD2 during DNA repair. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 27, Issue 3, Page 240-248, Year 2020 |
掲載日 | 2020年2月17日 |
著者 | Pablo Alcón / Shabih Shakeel / Zhuo A Chen / Juri Rappsilber / Ketan J Patel / Lori A Passmore / |
PubMed 要旨 | Vertebrate DNA crosslink repair excises toxic replication-blocking DNA crosslinks. Numerous factors involved in crosslink repair have been identified, and mutations in their corresponding genes cause ...Vertebrate DNA crosslink repair excises toxic replication-blocking DNA crosslinks. Numerous factors involved in crosslink repair have been identified, and mutations in their corresponding genes cause Fanconi anemia (FA). A key step in crosslink repair is monoubiquitination of the FANCD2-FANCI heterodimer, which then recruits nucleases to remove the DNA lesion. Here, we use cryo-EM to determine the structures of recombinant chicken FANCD2 and FANCI complexes. FANCD2-FANCI adopts a closed conformation when the FANCD2 subunit is monoubiquitinated, creating a channel that encloses double-stranded DNA (dsDNA). Ubiquitin is positioned at the interface of FANCD2 and FANCI, where it acts as a covalent molecular pin to trap the complex on DNA. In contrast, isolated FANCD2 is a homodimer that is unable to bind DNA, suggestive of an autoinhibitory mechanism that prevents premature activation. Together, our work suggests that FANCD2-FANCI is a clamp that is locked onto DNA by ubiquitin, with distinct interfaces that may recruit other DNA repair factors. |
リンク | Nat Struct Mol Biol / PubMed:32066963 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 - 4.1 Å |
構造データ | EMDB-10531, PDB-6tnf: EMDB-10532, PDB-6tng: EMDB-10534, PDB-6tni: |
由来 |
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キーワード | DNA BINDING PROTEIN (DNA結合タンパク質) / Fanconi anaemia (ファンコーニ貧血) / ubiquitin (ユビキチン) / DNA repair (DNA修復) / DNA damage (DNA修復) / inter-strand crosslink |