Aldh2−/−Fancd2−/− mice develop severe HSC attrition, causing spontaneous bone marrow failure, which can also be induced by exposing these mice to ethanol5,6. This genetic interaction suggests that in the absence of aldehyde catabolism (such as in Aldh2−/− mice), DNA repair is engaged to maintain blood homeostasis. To test this theory, we set out to monitor DNA repair activity in vivo. The Fanconi anaemia pathway repairs DNA crosslinks by using a replication-coupled excision mechanism that is completed by homologous recombination14,15. We therefore used a method to visualize sister-chromatid exchange (SCE) events in bone marrow cells of living mice; these represent recombination repair transactions coupled to replication (Fig. 1a). The number of SCE events is elevated 2.3-fold in Aldh2−/− mice, indicating that recombination repair is stimulated in response to endogenous aldehydes (Fig. 1b, c). Moreover, a single exposure to alcohol causes a fourfold increase in SCE events in Aldh2−/− mice (Fig. 1b, c, Extended Data Fig. 1a), suggesting that physiological acetaldehyde accumulation in blood cells is not sufficient to inactivate the homologous recombination repair factor BRCA216. Fancd2−/− mice do not show similar
