DNA damage sensing by the ATM and ATR kinases.
Alexandre Maréchal,Lee Zou +1 more
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TLDR
The recent findings and current models of how ATM and ATR senseDNA damage, how they are activated by DNA damage, and how they function in concert to regulate the DDR are discussed.Abstract:
In eukaryotic cells, maintenance of genomic stability relies on the coordinated action of a network of cellular processes, including DNA replication, DNA repair, cell-cycle progression, and others. The DNA damage response (DDR) signaling pathway orchestrated by the ATM and ATR kinases is the central regulator of this network in response to DNA damage. Both ATM and ATR are activated by DNA damage and DNA replication stress, but their DNA-damage specificities are distinct and their functions are not redundant. Furthermore, ATM and ATR often work together to signal DNA damage and regulate downstream processes. Here, we will discuss the recent findings and current models of how ATM and ATR sense DNA damage, how they are activated by DNA damage, and how they function in concert to regulate the DDR.read more
Citations
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Journal ArticleDOI
Causes and consequences of replication stress.
TL;DR: In this paper, the kinase ATR (ATM- and Rad3-related) stabilizes and helps to restart stalled replication forks, avoiding the generation of DNA damage and genome instability.
Journal ArticleDOI
Targeting DNA Repair in Cancer: Beyond PARP Inhibitors.
TL;DR: A thorough understanding of DDR pathway complexities must be combined with strategies and lessons learned from the successful registration of PARP inhibitors in order to fully exploit the potential of DDR inhibitors and to ensure their long-term clinical success.
Journal ArticleDOI
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Ruchi Kumari,Parmjit S Jat +1 more
TL;DR: In this article, the molecular mechanisms that underlie cellular senescence and the senescent associated growth arrest with a particular focus on why cells stop dividing, the stability of the growth arrest, the hypersecretory phenotype and how the different pathways are all integrated.
Journal ArticleDOI
RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response.
Alexandre Maréchal,Lee Zou +1 more
TL;DR: The current understanding of the critical functions of the RPA-ssDNA platform in the maintenance of genome stability and its regulation through an elaborate network of covalent modifications is reviewed.
Journal ArticleDOI
CHK2 kinase in the DNA damage response and beyond
TL;DR: The activity of CHK2 in response to DNA damage and in the maintenance of the biological functions in unstressed cells are discussed and their activities are considered in relation to a possible role of CHk2 in tumorigenesis and, as a consequence, in the target of cancer therapy.
References
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Megan Fabbro,Kienan I. Savage,Kienan I. Savage,Karen Hobson,Andrew J. Deans,Simon N. Powell,Grant A. McArthur,Kum Kum Khanna +7 more
TL;DR: It is demonstrated that the BRCA1-BARD1 complex is required for ATM/ATR (ataxia-telangiectasia-mutated/ATM and Rad3-related)-mediated phosphorylation of p53Ser-15 following IR- and UV radiation-induced DNA damage.
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Targeting radiation-resistant hypoxic tumour cells through ATR inhibition
Isabel M. Pires,Monica M. Olcina,Selvakumar Anbalagan,John Pollard,Philip Michael Reaper,Peter A. Charlton,W G McKenna,Ester M. Hammond +7 more
TL;DR: Findings suggest that ATR inhibition represents a novel strategy to target tumour cells in conditions relevant to pathophysiology and enhance the efficacy of radiotherapy.
Journal ArticleDOI
Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity.
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