Fanconi anemia (FA) is a human genetic disorder characterized by 
hypersensitivity to DNA crosslinking agents. Its cellular phenotypes include 
increased chromosome breakage and a marked cell-cycle delay with 4N DNA content 
after introduction of interstrand DNA crosslinks (ICL). To further understand 
the nature of this delay previously described as a G2/M arrest, we introduced 
ICL specifically during G2 and monitored the cells for passage into mitosis. Our 
results showed that, even at the highest doses, postreplication ICL produced 
neither G2/M arrest nor chromosome breakage in FA-A or FA-C cells. This suggests 
that, similar to wild-type cells, DNA replication is required to trigger both 
responses. Therefore, the 4N cell DNA content observed in FA cells after ICL 
treatment also represents incomplete DNA replication and arrest in late S phase. 
FA fibroblasts from complementation groups A and C were able to recover from the 
ICL-induced cell-cycle arrest, but took approximately 3 times longer than 
controls. These results indicate that the FA pathway is required for the 
efficient resolution of ICL-induced S-phase arrest.