Figure 5.—

The genetic structure of the S-phase DNA damage pathway and a model for its function. (A) The placement of MRN in the epistasis relationship of the genes involved in checkpoint-dependent slowing of replication (Willis and Rhind 2009). The mus81Δ rhp51Δ double mutant has the same slowing-defective phenotype as mus81Δ, thus mus81Δ is epistatic to rhp51Δ. Likewise, the rqh1Δ rhp51Δ double mutant has the same slowing-proficient phenotype as rhp51Δ, thus rhp51Δ is epistatic to rqh1Δ. The analysis in this article places the MRN mutations in epistasis group III with rqh1Δ and sfr1Δ. However, the additive nature of the sfr1Δ and nbs1Δ phenotypes allow us to subdivide the group into subgroups IIIA and IIIB. (B) A model for the checkpoint-dependent regulation of replication slowing. Cds1 induces Mus81-dependent slowing. However, this slowing requires Rhp51-dependent recombination be held in check by a combination of MRN, Sfr1, and Rqh1.