Fanconi anemia (FA) is a recessive cancer prone syndrome featuring bone marrow 
failure and hypersensitivity to DNA interstrand crosslinks (ICLs) and, to a 
milder extension, to ionizing radiation and oxidative stress. Recently, we 
reported that human oxidative DNA glycosylase, NEIL1 excises with high 
efficiency the unhooked crosslinked oligomer within three-stranded DNA repair 
intermediate induced by photoactivated psoralen exposure. Complete 
reconstitution of repair of the ICL within a three-stranded DNA structure shows 
that it is processed in the short-patch base excision repair (BER) pathway. To 
examine whether the DNA damage hypersensitivity in FA cells follows impaired BER 
activities, we measured DNA glycosylase and AP endonuclease activities in 
cell-free extracts from wild-type, FA, and FA-corrected cells. We showed that 
immortalized lymphoid cells of FA complementation Groups A, C, and D and from 
control cells from normal donors contain similar BER activities. Intriguingly, 
the cellular level of NEIL1 protein strongly depends on the intact FA pathway 
suggesting that the hypersensitivity of FA cells to ICLs may, at least in part, 
arise from downregulation or degradation of NEIL1. Consistent with this result, 
plasmid-based expression of the FLAG-tagged NEIL1 protein partially complements 
the hypersensitivity FA cells to the crosslinking agents exposures, suggesting 
that NEIL1 specifically complements impaired capability of FA cells to repair 
ICLs and oxidative DNA damage. These findings shed light to how the FA pathway 
may regulate DNA repair proteins and bring explanation for the long-time 
disputed problem of the oxidative stress sensitive phenotype of FA cells.