Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
Abstract

Cells respond to DNA damage by activating a network of signaling pathways that control cell cycle progression and DNA repair. Genetic studies in yeast suggested that several checkpoint proteins, including the RFC-related Rad17 protein, and the PCNA-related Rad1–Rad9–Hus1 protein complex might function as sensors of DNA damage. In this study, we show that the human Rad17 protein recruits the Rad9 protein complex onto chromatin after damage. Rad17 binds to chromatin prior to damage and is phosphorylated by ATR on chromatin after damage but Rad17's phosphorylation is not required for Rad9 loading onto chromatin. The chromatin associations of Rad17 and ATR are largely independent, which suggests that they localize to DNA damage independently. Furthermore, the phosphorylation of Rad17 requires Hus1, suggesting that the Rad1–Rad9–Hus1 complex recruited by Rad17 enables ATR to recognize its substrates. Our data are consistent with a model in which multiple checkpoint protein complexes localize to sites of DNA damage independently and interact to trigger the checkpoint-signaling cascade.

Bibliography

Zou, L., Cortez, D., & Elledge, S. J. (2002). Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Genes & Development, 16(2), 198–208.

Authors 3
  1. Lee Zou (first)
  2. David Cortez (additional)
  3. Stephen J. Elledge (additional)
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Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 7:59 p.m.)
Deposited 3 years, 9 months ago (Nov. 15, 2021, 10:56 a.m.)
Indexed 1 month, 1 week ago (July 14, 2025, 11:44 p.m.)
Issued 23 years, 7 months ago (Jan. 15, 2002)
Published 23 years, 7 months ago (Jan. 15, 2002)
Published Online 23 years, 7 months ago (Jan. 15, 2002)
Published Print 23 years, 7 months ago (Jan. 15, 2002)
Funders 0

None

@article{Zou_2002, title={Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin}, volume={16}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.950302}, DOI={10.1101/gad.950302}, number={2}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Zou, Lee and Cortez, David and Elledge, Stephen J.}, year={2002}, month=jan, pages={198–208} }