Illustrative example of mechanistic modeling in FA. Schematic of the first two steps of ICL detection and repair, involving binding of the protein FANCM to the DNA, followed by recruitment of the FA core complex (A). For demonstration purposes, we have chosen to model the protein subcomplexes AG20, BL100, and CEF as independent species that reversibly bind to form the FA core complex. Note that this choice of model resolution is at the modeler’s discretion, i.e., alternatively, each protein (FANCA, FANCG, FAAP20, etc.) comprising the subcomplexes could have been modeled as independent species (B). Eight reversible biochemical interactions (16 reactions total) can describe the ICL detection and FA core complex recruitment process (C). In silico time courses for different molecular species can be obtained by setting values of the binding/unbinding rate constants (all set to 1 in this case) and numerically integrating the resultant set of coupled ODEs (D). ‘FANCM_free’: unbound FANCM; ‘FANCM_ICL’: FANCM bound to the DNA around the ICL; ‘FA_complex’: FA core complex composed of AG20, BL100, and CEF that is not bound to FANCM; ‘FAcpx_M_ICL’: FA core complex bound to FANCM, which is bound to the ICL.