The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder.
Mutations in any of at least sixteen FANC genes (FANCA-Q) cause Fanconi anemia, a disorder characterized by sensitivity to DNA interstrand crosslinking agents. The clinical features of cytopenia, developmental defects, and tumor predisposition are similar in each group, suggesting that the gene products participate in a common pathway. The Fanconi anemia DNA repair pathway consists of an anchor complex that recognizes damage caused by interstrand crosslinks, a multisubunit ubiquitin ligase that monoubiquitinates two substrates, and several downstream repair proteins including nucleases and homologous recombination enzymes. We review progress in the use of structural and biochemical approaches to understanding how each FANC protein functions in this pathway.
MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom; email: H.walden@dundee.ac.uk.
Helen
H
Walden
Andrew J
AJ
Deans
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D005199:Fanconi Anemia / Q000378:metabolism*; D052217:Fanconi Anemia Complementation Group A Protein / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics
D052217:Fanconi Anemia Complementation Group A Protein; D009687:Nuclear Proteins; D025801:Ubiquitin
DNA repair; Fanconi anemia; interstrand crosslink; structural biology; ubiquitin ligase