Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA 
repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous 
spectrum of clinical features. The most significant and consistent phenotypic 
characteristics are stem cell loss, causing progressive bone marrow failure and 
sterility, diverse developmental abnormalities and a profound predisposition to 
neoplasia. To date, 15 genes have been identified, biallelic disruption of any 
one of which results in this clinically defined syndrome. It is now apparent 
that all 15 gene products act in a common process to maintain genome stability. 
At the molecular level, a fundamental defect in DNA repair underlies this 
complex phenotype. Cells derived from FA patients spontaneously accumulate 
broken chromosomes and exhibit a marked sensitivity to DNA-damaging 
chemotherapeutic agents. Despite complementation analysis defining many 
components of the FA DNA repair pathway, no direct link to DNA metabolism was 
established until recently. First, it is now evident that the FA pathway is 
required to make incisions at the site of damaged DNA. Second, a specific 
component of the FA pathway has been identified that regulates nucleases 
previously implicated in DNA interstrand crosslink repair. Taken together, these 
data provide genetic and biochemical evidence that the FA pathway is a bona fide 
DNA repair pathway that directly mediates DNA repair transactions, thereby 
elucidating the specific molecular defect in human Fanconi anaemia.