This blog focuses on a 2010 Nature Structural & Molecular Biology paper by London-based researchers Ambrose R. Cole, Laurence P. C. Lewis and Helen Walden. The study identifies the structural basis of the autosomal recessive disorder Fanconi anemia (FA). Specifically, the structure of FANCL, the catalytic subunit of the Fanconi anemia core complex.The FA core complex monoubiquitinates a FANCI-FANCD2 complex, allowing recruitment of factors requried to repair DNA damage. (FANCI-FANCD2 may aid repair of damaged replication forks due to its preferential recognition of branched structures).
Thirteen protiens comprise the FA complex. A lack of structural information has made identifying the cascade in which they interact to initiate DNA repair difficult. Using Drosophila, the crystal structure of FANCL was determined. Subsequent efforts were made to identify how FANCL is arranged to bind E2-like folds/substrate, and most importantly how it is able to monoubiquitnate FANCD2.
This blog is a summary and analysis of their methods and results.
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