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Fig. 5. Rad17 phosphorylation at Ser635 and Ser645 decreases the mobility of GFP-Rad9 in damage-induced foci. U2OS cells expressing GFP-Rad9 were transfected with Flag-Rad17 or Flag-Rad17^AA constructs, together with mCherry-C1, to detect transfected cells. Cells were left untreated (UNT) or treated with UV and FLIP-FRAP analysis was performed on red cells. (A) Quantification of FLIP and FRAP as described in Fig. 4B. (B) Difference in relative fluorescence, plotted against time, as described in Fig. 4C. (C) ATR and Rad17 collaborate in modulating Rad9 localisation at sites of DNA damage. ssDNA generated as a result of DNA damage or replication stress is recognised by RPA (1). Recognition of ssDNA by RPA leads to the independent recruitment of ATR and Rad17 to DNA lesions. Rad17 loads the 9-1-1 complex at sites of ssDNA and facilitates activation of ATR through an interaction with TopBP1 (2). ATR subsequently phosphorylates Claspin, which acts to recruit Chk1 and promote its phosphorylation by ATR. ATR also phosphorylates Rad17 (3). ATR-mediated phosphorylation of Rad17 stabilises the 9-1-1 complex at sites of DNA lesions. This could in turn result in the maintenance of activated ATR and continued checkpoint signalling until DNA damage is repaired (4).

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