Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, 
characterized by genomic instability and hypersensitivity to DNA cross-linking 
agents. The discovery of biallelic BRCA2 mutations in the FA-D1 complementation 
group allows for the first time to study the characteristics of primary 
BRCA2-deficient human cells. FANCD1/BRCA2-deficient fibroblasts appeared 
hypersensitive to mitomycin C (MMC), slightly sensitive to methyl methane 
sulfonate (MMS), and like cells derived from other FA complementation groups, 
not sensitive to X-ray irradiation. However, unlike other FA cells, FA-D1 cells 
were slightly sensitive to UV irradiation. Despite the observed lack of X-ray 
sensitivity in cell survival, significant radioresistant DNA synthesis (RDS) was 
observed in the BRCA2-deficient fibroblasts but also in the FANCA-deficient 
fibroblasts, suggesting an impaired S-phase checkpoint. FA-D1/BRCA2 cells 
displayed greatly enhanced levels of spontaneous as well as MMC-induced 
chromosomal aberrations (CA), similar to cells deficient in homologous 
recombination (HR) and non-D1 FA cells. In contrast to Brca2-deficient rodent 
cells, FA-D1/BRCA2 cells showed normal sister chromatid exchange (SCE) levels, 
both spontaneous as well as after MMC treatment. Hence, these data indicate that 
human cells with biallelic BRCA2 mutations display typical features of both FA- 
and HR-deficient cells, which suggests that FANCD1/BRCA2 is part of the 
integrated FA/BRCA DNA damage response pathway but also controls other functions 
outside the FA pathway.