ATR: An Essential Regulator of Genome Integrity

By Karlene A. Cimprich, D. Cortez. Nature reviews. Molecular cell biology, 2008

1,863 citations recorded by the source corpus.

Genome maintenance is a constant concern for cells, and a coordinated response to DNA damage is required to maintain cellular viability and prevent disease. The ataxia-telangiectasia mutated (ATM) and ATM and RAD3-related (ATR) protein kinases act as master regulators of the DNA-damage response by signalling to control cell-cycle transitions, DNA replication, DNA repair and apoptosis. Recent studies have provided new insights into the mechanisms that control ATR activation, have helped to explain the overlapping but non-redundant activities of ATR and ATM in DNA-damage signalling, and have clarified the crucial functions of ATR in maintaining genome integrity.

Subfields: Cell Biology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/656c045f05fd3861373b5f82395ed91d8a899138

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Citations in the corpus

The DNA Damage Response: Making it safe to play with knives (2010, background): “It is the colocalization of these two RPA-dependent complexes that sets in motion the ATR signaling cascade, which results in the activation of CHK1 and CHK2 kinase signaling and phosphorylation of many chromatin bound factors to promote fork stability and restart of stalled or collapsed replication”
DNA replication stress as a hallmark of cancer. (2015, background): “ATR phosphorylates several substrates, including the checkpoint kinase Chk1 and the single-stranded DNA binding protein RPA to regulate cell cycle progression and the stability of replication forks under stress (71).”
The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. (2010, background): “As with ATM, ATR is also thought to act on many other substrates in addition to Chk1, including BRCA1, mini-chromosome maintenance (MCM) proteins, and components of the RPA complex (Cimprich and Cortez, 2008).”
Mechanisms and pathways of growth failure in primordial dwarfism. (2011, background): “However, unlike ATM, ATR is an essential gene, due to its role in either regulating orderly cell cycle progression from S phase to mitosis or constitutively stabilizing stalled replication forks that arise physiologically in unperturbed cells (Cimprich and Cortez 2008).”
How shelterin solves the telomere end-protection problem. (2010, background): “For primary references and more extensive details on these pathways, the reader is referred to excellent recent reviews on these subjects (Hefferin and Tomkinson 2005; Harper and Elledge 2007; Cimprich and Cortez 2008; Jackson and Bartek 2009; Mahaney et al. 2009; Mimitou and Symington 2009; Lieber ”
Cell cycle, CDKs and cancer: a changing paradigm (2009, background): “The molecular pathways that prevent cells from proliferating until damaged DNA has been properly repaired have been extensively reviewe”
Tumor Exome Analysis Reveals Neoantigen-Specific T-Cell Reactivity in an Ipilimumab-Responsive Melanoma (2013, background): “3A, pMHC, peptide MHC, PE-Cy7, R-Phycoerythrincyanine 7; QD 625, Qdot 625; WT, wildtype) against a mutated epitope in the ATR serine/ threonine protein kinase that functions to signal DNA damage (20).”
DNA damage sensing by the ATM and ATR kinases. (2013, background): “…events may protect the genome during DNA synthesis by regulating nucleotide levels, fork progression, origin firing, and cell-cycle transitions, and activating specific DNA repair pathways to promote complete and accurate replication of the genome (Cimprich and Cortez 2008; Flynn and Zou 2011).”