Discovery of a FANCD2-interacting protein motif (DIP-box) linking DNA Damage Response processes

Abstract Repair of DNA damage is critical to genome integrity and the DNA clamp, FANCD2, is a major player in the response to interstrand crosslinks tying the two DNA strands together. It has long been suggested FANCD2 recruits other factors to coordinate repair these crosslinks, however it remains unclear if FANCD2 directly mediates this and how this is achieved. Here we show that FANCD2 has a conserved acidic region that directly recognises established DNA repair proteins containing a short linear motif. We discover new candidate interactors engaging with FANCD2 in a similar mode that are involved in histone modification, and RNA processing. Our data demonstrate FANCD2 is a hub for protein-protein interactions providing a structural explanation for FANCD2’s central role in repair of DNA interstrand crosslinks. Competing Interest Statement The authors have declared no competing interest. Footnotes This version has been revised to include cellular data demonstrating the effect of disrupting the DIP-box binding site on FANCD2.