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ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks
Abstract
It is generally thought that the DNA-damage checkpoint kinases, ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), work independently of one another. Here, we show that ATM and the nuclease activity of meiotic recombination 11 (Mre11) are required for the processing of DNA double-strand breaks (DSBs) to generate the replication protein A (RPA)-coated ssDNA that is needed for ATR recruitment and the subsequent phosphorylation and activation of Chk1. Moreover, we show that efficient ATM-dependent ATR activation in response to DSBs is restricted to the S and G2 cell cycle phases and requires CDK kinase activity. Thus, in response to DSBs, ATR activation is regulated by ATM in a cell-cycle dependent manner.
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“The situation is somewhat complicated by the finding that ATR can be also recruited to DSBs and this binding depends upon ATM [41,42].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [41]
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“Furthermore, ATM is essential for DSB-induced ATR activation in the S and G2 phases of cell cycle, but not in the G1 phase [140].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [140]
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Metadata
- Authors
- Jazayeri, A., Falck, J., Lukas, C., Bartek, J., Smith, G. C. M., Lukas, J., & Jackson, S. P.
- Affiliations
- University of Cambridge (GB)
- Danish Cancer Society (DK)
- Corresponding author
- Jackson, Stephen P.
- Venue
- Nature Cell Biology
- Published
- 2005-12-04
- Volume
- 8
- Issue
- 1
- Pages
- 37-45
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2062284662
- Cited by
- 1,064
- References
- 47
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 24 · 2023: 17 · 2022: 33 · 2021: 43 · 2020: 35 · 2019: 45 · 2018: 38 · 2017: 41 · 2016: 48 · 2015: 64 · 2014: 56 · 2013: 79 · 2012: 65
- FWCI
- 25.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- ATM, ATR, DNA double-strand breaks, DNA damage checkpoint, Mre11 nuclease, Chk1 phosphorylation, cell cycle regulation, meiotic recombination
- MeSH terms
- Checkpoint Kinase 1, MRE11 Homologue Protein, Cell Cycle, Cell Nucleus, DNA Damage, DNA-Binding Proteins, HeLa Cells, Humans, Nuclear Proteins, Phosphorylation, Protein Kinases, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Cyclin-Dependent Kinases, Tumor Suppressor Proteins, Cell Line, Tumor, Replication Protein A, Ataxia Telangiectasia Mutated Proteins
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