FA proteins (shown as lettered ovals) exist in various multimeric complexes in the cytoplasm and nucleus. The nuclear core complex facilitates the monoubiquitination (Ub) of FANCD2 (D2) protecting cells from genetic damage and death following exposure to cross-linking agents. Cytoplasmic complexes are also found, and there is emerging evidence that various FA complexes, often acting in concert with heat shock proteins, function to suppress the activation state of intracellular effectors of apoptosis (promoting survival) and facilitate survival signaling pathways including those that involve JAK-dependent STAT activation (promoting survival). Thus, FA cells are intolerant of a variety of extracellular stresses, not just cross-linking agents. The nuclear core complex shown is known to exist. The exact composition of the cytoplasmic FA complexes has not been fully defined, so in this figure the complex shown is meant to be generically reflective of multiple subcomplexes that are known to exist and of subcomplexes that will be identified in the future. Illustration by Marie Dauenheimer.