Mechanisms for synthetic genetic interactions proposed by Kaelin . Each node or circle is a multi-protein complex. Synthetic genetic interactions between members of the multi-protein complexes are presented by red lines. Synthetic lethality in loss-of-function alleles can arise from at least four different mechanisms. (a) The cellular organizational units might be uniquely redundant with respect to an essential function; multi-protein complexes A and A' might share paralogues. (b) They might be two sub-units of an essential multi-protein complex: a-c form a sub-complex and synthetically interact with e-h. (c) They might be two interconnected components in an essential linear pathway: each mutation decreases the flow through the pathway. (d) They might participate in parallel pathways that are together essential: one pathway might be needed to compensate for the damage caused by mutations in the other pathway.