BRCA2 loss in Fanconi Anemia

Fanconi Anemia (FA) is a recessive cancer susceptibility syndrome. Six FA genes have been cloned and encode proteins involved in a DNA-damage response pathway. In the June 13 ScienceXpress, Niall Howlett and colleagues report the characterization of mutations in cells from the FA subtypes B and D1 (ScienceXpress 2002, DOI:10.1126/science.1073834).

They discovered biallelic mutations in the BRCA2 breast cancer susceptibility gene; the mutations create frameshifts resulting in truncated BRCA2 protein. Howlett et al. show that restoring BRCA2 expression could rescue the phenotype of FA cells and restore resistance to DNA-damaging agents. The authors propose a model linking FA-associated genes to the regulation of a common DNA-damage response pathway.