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Medline ® Abstract for Reference 40

of 'Clinical manifestations and diagnosis of Fanconi anemia'

What is the DNA repair defect underlying Fanconi anemia?
Duxin JP, Walter JC
Curr Opin Cell Biol. 2015 Dec;37:49-60. Epub 2015 Nov 11.
Fanconi anemia (FA) is a rare human genetic disease characterized by bone marrow failure, cancer predisposition, and genomic instability. It has been known for many years that FA patient-derived cells are exquisitely sensitive to DNA interstrand cross-linking agents such as cisplatin and mitomycin C. On this basis, it was widely assumed that failure to repair endogenous interstrand cross-links (ICLs) causes FA, although the endogenous mutagen that generates these lesions remained elusive. Recent genetic evidence now suggests that endogenous aldehydes are the driving force behind FA. Importantly, aldehydes cause a variety of DNA lesions, including ICLs and DNA protein cross-links (DPCs), re-kindling the debate about which DNA lesions cause FA. In this review, we discuss new developments in our understanding of DPC and ICL repair, and how these findings bear on the question of which DNA lesion underlies FA.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.