Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, 
characterized by genomic instability, hypersensitivity to DNA cross-linking 
agents, and a prolonged G2 phase of the cell cycle. We observed a marked 
dose-dependent accumulation of FA cells in the G2 compartment after treatment 
with 4,5',8-trimethylpsoralen (Me(3)Pso) in combination with 365 nm irradiation. 
Using bivariate DNA distribution methodology, we determined the proportion of 
replicating and arresting S-phase cells and observed that, whereas normal cells 
arrested DNA replication in the presence of Me(3)Pso cross-links and 
monoadducts, FA lymphoblasts failed to arrest DNA synthesis. Taken together, the 
above data suggest that, in response to damage induced by DNA cross-linking 
agents, the S-phase checkpoint is inefficient in FA cells. This would lead to 
accumulation of secondary lesions, such as single- and double-strand breaks and 
gaps. The prolonged time in G2 phase seen in FA cells therefore exists in order 
to allow the cells to remove lesions which accumulated during the preceding 
abnormal S phase.