Fig. 3.

Diagram of the main posttranslational modification events involved in the activation of response to ICLs. Once the ICL is detected it triggers the ATR/Chk1 pathway leading to the phosphorylation of several components of the FA core complex. ATR and potentially other kinases phosphorylate FANCI and FANCD2 (1) priming the complex for its monoubiquitination. These phosphorylation events lead then to the monoubiquitination of the FANCD2/FANCI complex by FANCL/UBE2T (2), which promotes its recruitment onto chromatin and the action of the effector proteins. On the other hand, the dosage of the FANCD2/FANCI complex on chromatin can be regulated through SUMOylation-dependent polyubiquitination mediated by PIAS1/4, UBC9 and RNF4 (3, 4). Finally, these events can be reversed by the action of a hypothetical deubiquitinase (5), SENP6 (6), the deubiquitinating enzyme USP1/UAF1 complex (7) as well as putative phosphatases (8) still unidentified