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• W2120897498 abstract "Rad17 is critical for the ATR-dependent activation of Chk1 during checkpoint responses. It is known that Rad17 loads the Rad9-Hus1-Rad1 (9-1-1) complex onto DNA. We show that Rad17 also mediates the interaction of 9-1-1 with the ATR-activating protein TopBP1 in Xenopus egg extracts. Studies with Rad17 mutants indicate that binding of ATP to Rad17 is essential for the association of 9-1-1 and TopBP1. Furthermore, hydrolysis of ATP by Rad17 is necessary for the loading of 9-1-1 onto DNA and the elevated, checkpoint-dependent accumulation of TopBP1 on chromatin. Significantly, a mutant 9-1-1 complex that cannot bind TopBP1 has a normal capacity to promote elevated accumulation of TopBP1 on chromatin. Taken together, we propose the following mechanism. First, Rad17 loads 9-1-1 onto DNA. Second, TopBP1 accumulates on chromatin in a manner that depends on both Rad17 and 9-1-1. Finally, 9-1-1 and TopBP1 dock in a Rad17-dependent manner before activation of Chk1." @default.
• W2120897498 created "2016-06-24" @default.
• W2120897498 creator A5005318646 @default.
• W2120897498 creator A5087914047 @default.
• W2120897498 date "2010-03-15" @default.
• W2120897498 modified "2023-10-11" @default.
• W2120897498 title "Rad17 Plays a Central Role in Establishment of the Interaction between TopBP1 and the Rad9-Hus1-Rad1 Complex at Stalled Replication Forks" @default.
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• W2120897498 doi "https://doi.org/10.1091/mbc.e09-11-0958" @default.
• W2120897498 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2836973" @default.
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