The essential kinase ATR: ensuring faithful duplication of a challenging genome
By J. Saldivar, D. Cortez, Karlene A. Cimprich. Nature reviews. Molecular cell biology, 2017
740 citations recorded by the source corpus.
One way to preserve a rare book is to lock it away from all potential sources of damage. Of course, an inaccessible book is also of little use, and the paper and ink will continue to degrade with age in any case. Like a book, the information stored in our DNA needs to be read, but it is also subject to continuous assault and therefore needs to be protected. In this Review, we examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells. We discuss the multiple data that have revealed an elegant yet increasingly complex mechanism of ATR activation. This involves a core set of components that recruit ATR to stressed replication forks, stimulate kinase activity and amplify ATR signalling. We focus on the activities of ATR in the control of cell cycle checkpoints, origin firing and replication fork stability, and on how proper regulation of these processes is crucial to ensure faithful duplication of a challenging genome.
Subfields: Cancer Research, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/3326773a55420ed0682818b9f0aabe117078b12b
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Citations in the corpus
- Doxorubicin—An Agent with Multiple Mechanisms of Anticancer Activity (2023, background): “Furthermore, additional factors including the MRE11–RAD50–NBS1 (MRN) complex and RAD9, RAD1, HUS1 interacting nuclear orphan (RHINO) may be involved in the recruitment of TOPBP1 for efficient activation of the ATR kinase [74].”
- R-loops as cellular regulators and genomic threats (2019, background): “As central regulators of the DNA damage response (DDR), the ATR and ATM protein kinases orchestrate responses to replication fork slowdown or stalling (replication stress), and to DSBs respectively (Blackford and Jackson, 2017; Saldivar et al., 2017).”
- Mitotic CDK promotes replisome disassembly, fork breakage, and complex DNA rearrangements (2018, background): “…the checkpoint kinase ATR supports cell 521 viability and suppression of replication fork collapse via phosphorylation of proteins at 522 the fork, no ATR substrates have been identified that definitively validate this 523 mechanism (Cortez, 2015; Pasero and Vindigni, 2017; Saldivar et al., 2017).”