Synthetic Lethality between Gene Defects Affecting a Single Non-essential Molecular Pathway with Reversible Steps
Figure 3
Abstract representation of the recombinational DNA repair pathway.
The scheme represents a simplified version of the pathway depicted in Figure S1 in Text S1 using the same abbreviations. Dynamic states S, I, P represent DNA damage substrate (S), toxic intermediate (I), and the product of repair (P). F1 (e.g. Rad51), F2 (e.g. Rad54), R1 (e.g. Srs2), R2 (e.g. Mph1) are enzymes in the main pathway, and F3-EC represent enzymes in the compensatory pathway. ks signify the kinetic rates of the model state transition steps. The two types of synthetic lethality (SL) are indicated: Red Xs – classic scenario of between-pathway SL (e.g. BRCA1 or BRCA2 mutant and PARP inhibition); Green Xs – within-reversible-pathway SL between two mutations in genes acting in a single non-essential pathway leading to the accumulation of a toxic intermediate (e.g. srs2 rad54 double mutant). For more discussion see also Section S1 in Text S1.