The repair of aldehyde-induced DNA damage is therefore not limited to the Fanconi anaemia crosslink-repair pathway. As the recombination machinery is essential for mouse development, we used the isogenic chicken B-cell line DT40, which has been used to define the involvement of homologous recombination in crosslink repair14. DT40 cells carrying disruptions of key homologous recombination genes show hypersensitivity to acetaldehyde (Fig. 1d, e), in a similar way to cells lacking the Fanconi anaemia gene FANCC. To test the relationship between the Fanconi anaemia and homologous recombination pathways, we analysed the sensitivity of cells deficient in both FANCC and XRCC2. These cells showed the same sensitivity to cisplatin as the single knockout cells (Fig. 1f), but were much more sensitive to acetaldehyde (Fig. 1g), indicating that homologous recombination repair confers additional acetaldehyde resistance beyond that provided by Fanconi anaemia crosslink repair. In summary, detoxification provides the dominant protection mechanism against endogenous aldehydes; however, when aldehydes damage DNA, cells use both DNA-crosslink and homologous recombination repair.
