FIGURE 6.

Model for Claspin-mediated Phosphorylation of Chk1 by ATR. ATR-ATRIP may be recruited to DNA by several mechanisms, all of which eventually lead to enhanced kinase activity. Thus, TopBP1 recruits ATR-ATRIP to DNA containing bulky adducts (indicated by the triangle). Claspin binds to both DNA and Chk1 and increases the affinity of ATR for Chk1 through a mechanism that requires the Chk1-binding domain and the MRC1-like domain. Note that this is one mechanism by which ATR and its co-activators can be recruited to DNA. There are alternative pathways of recruiting ATR such as by RPA, mismatch repair proteins, and other factors. The circled P indicates phosphorylation.