ATM regulates ATR chromatin loading in response to DNA double-strand breaks
Open accessAbstract
DNA double-strand breaks (DSBs) are among the most deleterious lesions that can challenge genomic integrity. Concomitant to the repair of the breaks, a rapid signaling cascade must be coordinated at the lesion site that leads to the activation of cell cycle checkpoints and/or apoptosis. In this context, ataxia telangiectasia mutated (ATM) and ATM and Rad-3–related (ATR) protein kinases are the earliest signaling molecules that are known to initiate the transduction cascade at damage sites. The current model places ATM and ATR in separate molecular routes that orchestrate distinct pathways of the checkpoint responses. Whereas ATM signals DSBs arising from ionizing radiation (IR) through a Chk2-dependent pathway, ATR is activated in a variety of replication-linked DSBs and leads to activation of the checkpoints in a Chk1 kinase–dependent manner. However, activation of the G2/M checkpoint in response to IR escapes this accepted paradigm because it is dependent on both ATM and ATR but independent of Chk2. Our data provides an explanation for this observation and places ATM activity upstream of ATR recruitment to IR-damaged chromatin. These data provide experimental evidence of an active cross talk between ATM and ATR signaling pathways in response to DNA damage.
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ATM is essential for recruiting ATR to ionizing radiation-damaged chromatin and for Chk1 phosphorylation at serine 345.
“ATM is essential for the recruitment of ATR to IR-damaged chromatin and Chk1 phosphorylation at Serine 345 [139].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [139]
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- Authors
- Cuadrado, M., Martinez-Pastor, B., Murga, M., Toledo, L. I., Gutierrez-Martinez, P., Lopez, E., & Fernandez-Capetillo, O.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Genomic Instability Group, Spanish National Cancer Center, Madrid 28029, Spain
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-02-06
- Volume
- 203
- Issue
- 2
- Pages
- 297-303
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2118201
- OpenAlex
- W2149468013
- Cited by
- 232
- References
- 23
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 17 · 2018: 5 · 2017: 8 · 2016: 12 · 2015: 9 · 2014: 16 · 2013: 9 · 2012: 17
- FWCI
- 9.78
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- ATM kinase, ATR kinase, DNA double-strand breaks, chromatin loading, ionizing radiation, G2/M checkpoint, Chk2, Chk1, DNA damage signaling, DNA repair
- MeSH terms
- Checkpoint Kinase 1, Ataxia Telangiectasia, Cell Cycle, Cell Line, Transformed, Chromatin, DNA Damage, DNA Replication, DNA-Binding Proteins, Flow Cytometry, Gamma Rays, Humans, Phosphorylation, Protein Kinases, Signal Transduction, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Chromosome Breakage, Tumor Suppressor Proteins, Cell Line, Tumor, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 2
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