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TitleFANCD2-FANCI is a clamp stabilized on DNA by monoubiquitination of FANCD2 during DNA repair.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 3, Page 240-248, Year 2020
Publish dateFeb 17, 2020
AuthorsPablo Alcón / Shabih Shakeel / Zhuo A Chen / Juri Rappsilber / Ketan J Patel / Lori A Passmore /
PubMed AbstractVertebrate 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.
External linksNat Struct Mol Biol / PubMed:32066963 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 4.1 Å
Structure data

10531

6tnf

EMDB-10531, PDB-6tnf:
Structure of monoubiquitinated FANCD2 in complex with FANCI and DNA
Method: EM (single particle) / Resolution: 3.8 Å

10532

6tng

EMDB-10532, PDB-6tng:
Structure of FANCD2 in complex with FANCI
Method: EM (single particle) / Resolution: 4.1 Å

10534

6tni

EMDB-10534, PDB-6tni:
Structure of FANCD2 homodimer
Method: EM (single particle) / Resolution: 3.4 Å

Source
  • gallus gallus (chicken)
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN / Fanconi anaemia / ubiquitin / DNA repair / DNA damage / inter-strand crosslink

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