6TNI

Structure of FANCD2 homodimer

Summary for 6TNI

• Entry DOI: 10.2210/pdb6tni/pdb
• EMDB information: 10534
• Descriptor: Uncharacterized protein (1 entity in total)
• Functional Keywords: fanconi anaemia, ubiquitin, dna repair, dna damage, inter-strand crosslink, dna binding protein
• Biological source: Gallus gallus (Chicken)
• Total number of polymer chains: 2
• Total formula weight: 329462.69

Authors

Alcon, P.,Shakeel, S.,Passmore, L.A. (deposition date: 2019-12-08, release date: 2020-02-19, Last modification date: 2024-05-22)

Primary citation

Alcon, P.,Shakeel, S.,Chen, Z.A.,Rappsilber, J.,Patel, K.J.,Passmore, L.A.
FANCD2-FANCI is a clamp stabilized on DNA by monoubiquitination of FANCD2 during DNA repair.
Nat.Struct.Mol.Biol., 27:240-248, 2020

PubMed 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.

PubMed: 32066963
DOI: 10.1038/s41594-020-0380-1

Experimental method

ELECTRON MICROSCOPY (3.4 Å)