FIGURE 6.

A working model for the role of FANCI DNA binding in ICL repair. An equilibrium of FANCI and FANCD2 interaction exists to sense DNA damage level that stalls replication forks in a cell. When DNA damage level is high, more ID complex will be formed and bound to stalled replication forks. The phosphorylation of FANCI could promote ID complex formation. The ID complex bound to the stalled fork will then be monoubiquitinated by the translocating FA core and therefore recruits downstream factors to initiate repair. When the damage is repaired or when the cells are free of damage, FANCI and FANCD2 in the ID complex tend to dissociate from each other because of dephosphorylation and deubiquitination. The hypothesized tendency of balance shift is indicated by either boldface solid arrows (association) or broken thin arrows (dissociation). A question mark denotes that this step is fully hypothetical without any direct evidence. FANCI and FANCD2 are highlighted with orange. The FA core complex with 10 subunits is depicted using gray ovals with their FA group letters. FANCL is the ubiquitin ligase. Red zigzag line, interstrand cross-link. Blue circle with the letter P, phosphorylation. Red circle with Ub, monoubiquitination.