Herpes Simplex Virus Type 1 Single Strand DNA Binding Protein and Helicase/Primase Complex Disable Cellular ATR Signaling
Figure 1
Recruitment of ATR pathway proteins to sites of DNA damage in uninfected cells.
The ssDNA at sites of damage is coated by Replication protein A (RPA) and recruits ATR through a direct interaction with the ATR interacting protein (ATRIP). This RPA coated ssDNA also promotes the loading of the 9-1-1 (Rad9-Rad1-Hus1) checkpoint clamp by Rad17 onto the junction of the ss/dsDNA. TopBP1 is recruited via an interaction with the phosphorylated C-terminal tail of Rad9. TopBP1 then activates ATR kinase activity resulting in phosphorylation of Chk1, which is promoted by Claspin.