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- W3197803464 abstract "Mammalian cells use diverse pathways to prevent deleterious consequences during DNA replication, yet the mechanism by which cells survey individual replisomes to detect spontaneous replication impediments at the basal level, and their accumulation during replication stress, remain undefined. Here, we used single-molecule localization microscopy coupled with high-order-correlation image-mining algorithms to quantify the composition of individual replisomes in single cells during unperturbed replication and under replicative stress. We identified a basal-level activity of ATR that monitors and regulates the amounts of RPA at forks during normal replication. Replication-stress amplifies the basal activity through the increased volume of ATR-RPA interaction and diffusion-driven enrichment of ATR at forks. This localized crowding of ATR enhances its collision probability, stimulating the activation of its replication-stress response. Finally, we provide a computational model describing how the basal activity of ATR is amplified to produce its canonical replication stress response." @default.
- W3197803464 created "2021-09-13" @default.
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- W3197803464 date "2021-10-01" @default.
- W3197803464 modified "2023-09-26" @default.
- W3197803464 title "A basal-level activity of ATR links replication fork surveillance and stress response" @default.
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- W3197803464 doi "https://doi.org/10.1016/j.molcel.2021.08.009" @default.
- W3197803464 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8541912" @default.
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- W3197803464 hasPublicationYear "2021" @default.
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