Fanconi anemia is a rare genetic disease characterized by bone marrow failure, developmental abnormalities, and dramatically increased cancer susceptibility. Cells derived from Fanconi anemia patients are sensitive to agents that cause DNA interstrand cross-links (ICLs), which suggests that the FA pathway controls the repair of these DNA lesions. Knipscheer et al. found that two Fanconi anemia proteins, FANCI and FANCD2, could promote the DNA replication-coupled repair of ICLs in cell extracts. Specifically, the FANCI-FANCD2 complex was required for the incisions that unhook the cross-link and for the insertion of a nucleotide across from the damaged template base during lesion bypass.
P. Knipscheer, M. Räschle, A. Smogorzewska, M. Enoiu, T. V. Ho, O. D. Schärer, S. J. Elledge, J. C. Walter, The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair. Science 326, 1698–1701 (2009). [Abstract] [Full Text]