Multiple-Pathway Analysis of Double-Strand Break Repair Mutations in Drosophila
Figure 6
Decision Circuit for Breaks in Rr3
(A) The decision process is represented as distinct from any specific biochemical pathway. It is envisioned as proceeding from left to right. The first step is the placement of each DSB into one of two intermediate pools, labeled pool 1 and pool 2. Breaks in pool 1 can be repaired by either NHEJ or SSA, whereas those in pool 2 are handled by either HR-h or SSA. In addition, HR-s (not drawn) restores the I-SceI cut site, enabling another round of DSB formation and repair.
(B–G) Hypothesized effects on the decision circuit by mutant genotypes are shown. When one of the transitions in the circuit is inhibited by reduction of a gene product, use of the alternative route is increased. The sizes of circles surrounding the three measured outcomes, NHEJ, SSA, and HR-h, are meant to reflect the relative frequencies. No attempt was made to scale these circles precisely to the data, since each diagram represents several experiments and sets of estimates.
(H) Depicts decision circuit for cross 1, which differs from cross 2 by the absence of any opportunity for HR-h. The HR-s repairs are shown explicitly here and assumed to come from pool 2.
(I) Hypothesized effect of rad51 mutation in cross 1 is shown. Decreased HR-s repair results in more use of SSA. Since only two outcome types are measured in cross 1, the relative frequency of NHEJ is reduced through increased competition with SSA.