Human α spectrin II and the FANCA, FANCC, and FANCG proteins bind to DNA containing psoralen interstrand cross-links

Repair of DNA interstrand cross-links is a complex process critical to which is the identification of sites of damage by specific proteins. We have recently identified the structural protein nonerythroid alpha spectrin (alpha SpII Sigma*) as a component of a nuclear protein complex; in normal human cells which is involved in the repair of DNA interstrand cross-links and have shown that it forms a complex with the Fanconi anemia proteins FANCA, FANCC, and FANCG. Using DNA affinity chromatography, we now show that alpha SpII Sigma*, present in HeLa cell nuclei, specifically binds to DNA containing psoralen interstrand crosslinks and that the FANCA, FANCC, and FANCG proteins are bound to this damaged DNA as well. That spectrin binds directly to the cross-linked DNA has been shown using purified bovine brain spectrin (alpha SpII Sigma1/beta SpII Sigmal)(2). Binding of the Fanconi anemia (FA) proteins to the damaged DNA may be either direct or indirect via their association with alpha SpII Sigma*. These results demonstrate a role for a spectrin in the nucleus as well as a new function for this protein in the cell, an involvement in DNA repair. alpha SpII Sigma* may bind to cross-linked DNA and act as a scaffold to help in the recruitment of repair proteins to the site of damage and aid in their alignment and interaction with each other, thus enhancing the efficiency of the repair process.