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. 2022 Feb 7;12:820273. doi: 10.3389/fcimb.2022.820273

Figure 1.

Figure 1

Schematic representation of ICLs repair by the Fanconi Anemia pathway. The protein complex composed of FANCM-MHF1-MHF2 is recruited to the chromatin upon recognition of ICL damage. Then, FANCM is activated and allows the recruitment of the core complex of the FA pathway composed of: FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FAAP100, FAAP20 and FAAP24. The core complex contains an ubiquitin E3 ligase activity and is responsible for the monoubiquitylation of the ID2 complex composed of FANCI and FANCD2 proteins. Monoubiquitinylation of ID2 complex promotes the recruitment of the nucleases FANP, FANCQ and FAN1 and end resection at the DNA damage site. Depending on the cellular context, recruitment of downstream factors belonging to either Homologous Recombination (HR) or to Non-homologous End Joining (NHEJ) will finalize the repair.