Eight FA proteins (FANCA, B, C, E, F, G, L and M) and 6 associated factors (FAAP20, FAAP24, FAAP100, HES1, MHF1 and MFH2) form a nuclear core complex, which acts as ubiquitin ligase. In response to DNA damage or replication stress, nuclear core complex monoubiquitinates two other FA proteins, FANCD2 and FANCI, which then recruit other downstream FA proteins FANCD1, FANCJ, FANCN, FANCO and FANCQ to damaged DNA and involved in DNA repair, cell-cycle control to repair ICL lesions and to maintain genome stability.