FANCD2-FANCI is a clamp stabilized on DNA by monoubiquitination of FANCD2 during DNA repair.
Nat Struct Mol Biol
; 27(3): 240-248, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-32066963
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
DNA
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Ubiquitina
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Reparo do DNA
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Proteínas de Grupos de Complementação da Anemia de Fanconi
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Proteína do Grupo de Complementação D2 da Anemia de Fanconi
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article