9FFB

ss-dsDNA-FANCD2-FANCI complex

Summary for 9FFB

• Entry DOI: 10.2210/pdb9ffb/pdb
• EMDB information: 50353
• Descriptor: DNA (5'-D(P*GP*CP*AP*GP*CP*TP*GP*TP*CP*TP*AP*GP*AP*GP*AP*CP*AP*TP*CP*GP*AP*T)-3'), DNA (5'-D(P*CP*GP*AP*TP*GP*TP*CP*TP*CP*TP*AP*GP*AP*CP*AP*GP*CP*TP*GP*C)-3'), Fanconi anemia protein FANCD2, ... (4 entities in total)
• Functional Keywords: ss-dsdna-fancd2-fanci, fanconi anemia, d2-i complex, dna binding protein
• Biological source: Gallus gallus (chicken); More
• Total number of polymer chains: 4
• Total formula weight: 327075.99

Authors

Alcon, P.,Passmore, L.A. (deposition date: 2024-05-22, release date: 2024-07-31, Last modification date: 2024-10-02)

Primary citation

Alcon, P.,Kaczmarczyk, A.P.,Ray, K.K.,Liolios, T.,Guilbaud, G.,Sijacki, T.,Shen, Y.,McLaughlin, S.H.,Sale, J.E.,Knipscheer, P.,Rueda, D.S.,Passmore, L.A.
FANCD2-FANCI surveys DNA and recognizes double- to single-stranded junctions.
Nature, 632:1165-1173, 2024

PubMed Abstract: DNA crosslinks block DNA replication and are repaired by the Fanconi anaemia pathway. The FANCD2-FANCI (D2-I) protein complex is central to this process as it initiates repair by coordinating DNA incisions around the lesion. However, D2-I is also known to have a more general role in DNA repair and in protecting stalled replication forks from unscheduled degradation. At present, it is unclear how DNA crosslinks are recognized and how D2-I functions in replication fork protection. Here, using single-molecule imaging, we show that D2-I is a sliding clamp that binds to and diffuses on double-stranded DNA. Notably, sliding D2-I stalls on encountering single-stranded-double-stranded (ss-ds) DNA junctions, structures that are generated when replication forks stall at DNA lesions. Using cryogenic electron microscopy, we determined structures of D2-I on DNA that show that stalled D2-I makes specific interactions with the ss-dsDNA junction that are distinct from those made by sliding D2-I. Thus, D2-I surveys dsDNA and, when it reaches an ssDNA gap, it specifically clamps onto ss-dsDNA junctions. Because ss-dsDNA junctions are found at stalled replication forks, D2-I can identify sites of DNA damage. Therefore, our data provide a unified molecular mechanism that reconciles the roles of D2-I in the recognition and protection of stalled replication forks in several DNA repair pathways.

PubMed: 39085614
DOI: 10.1038/s41586-024-07770-w

Experimental method

ELECTRON MICROSCOPY (3.59 Å)