Regulation of the Fanconi anemia pathway Authored: Matthews, L, 2009-05-02 17:26:55 Edited: Matthews, L, 2009-05-20 15:51:04 Pubmed16916645 Pubmed16943440 Pubmed18082604 Pubmed18931676 Reactome Database ID Release 43419552 Reactome, http://www.reactome.org ReactomeREACT_18265 Reviewed: Huang, TT, 2009-05-20 17:48:24 The Fanconi anemia DNA repair pathway is negatively regulated by the deubiquitination of FANCD2 an postively regulated by phosphorylation of the FANCD2 and FANCI. The USP1 deubiquitinating enzyme is responsible for FANCD2 deubiquitination and is activated by the WD40-repeat containing UAF1 protein through formation of a stable USP1/UAF1 protein complex (Cohn et al., 2007). ATR and ATM dependent phosphorylation of FANCD2 at T691 and S717 promotes the monoubiquitination of FANCD2 stimulating the FA pathway (Ho et al., 2006). Multiple phosphorylation sites within FANCI are functionally important for inducing monoubiquitination of FANCD2 and thus the activation of the FA pathway (Ishiai et al., 2008) . PathwayStep3014 PathwayStep3016 PathwayStep3015 Phosphorylation of FANCD2 by ATR/ATM FANCD2 deubiquitination by USP1/UAF1 Phosphorylation of FANCI by ATM/ATR